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Sample records for bronchial-associated lymphoid tissue

  1. Pulmonary infections in swine induce altered porcine surfactant protein D expression and localization to dendritic cells in bronchial-associated lymphoid tissue

    PubMed Central

    Soerensen, Charlotte M; Holmskov, Uffe; Aalbaek, Bent; Boye, Mette; Heegaard, Peter M; Nielsen, Ole L

    2005-01-01

    Surfactant protein D (SP-D) is a pattern-recognition molecule of the innate immune system that recognizes various microbial surface-specific carbohydrate and lipid patterns. In vitro data has suggested that this binding may lead to increased microbial association with macrophages and dendritic cells. The aim of the present in vivo study was to study the expression of porcine SP-D (pSP-D) in the lung during different pulmonary bacterial infections, and the effect of the routes of infection on this expression was elucidated. Furthermore, the aim was to study the in vivo spatial relationship among pSP-D, pathogens, phagocytic cells and dendritic cells. Lung tissue was collected from experimental and natural bronchopneumonias caused by Actinobacillus pleuropneumoniae or Staphylococcus aureus, and from embolic and diffuse interstitial pneumonia, caused by Staph. aureus or Arcanobacterium pyogenes and Streptococcus suis serotype 2, respectively. By comparing normal and diseased lung tissue from the same lungs, increased diffuse pSP-D immunoreactivity was seen in the surfactant in both acute and chronic bronchopneumonias, while such increased expression of pSP-D was generally not present in the interstitial pneumonias. Co-localization of pSP-D, alveolar macrophages and bacteria was demonstrated, and pSP-D showed a patchy distribution on the membranes of alveolar macrophages. SP-D immunoreactivity was intracellular in dendritic cells. The dendritic cells were identified by their morphology, the absence of macrophage marker immunoreactivity and the presence of dendritic cell marker immunoreactivity. Increased expression of pSP-D in the surfactant coincided with presence of pSP-D-positive dendritic cells in bronchus-associated lymphoid tissue (BALT), indicating a possible transport of pSP-D through the specialized M cells overlying (BALT). In conclusion, we have shown that pSP-D expression in the lung surfactant is induced by bacterial infection by an aerogenous route rather

  2. BRONCHIAL LESIONS OF MOUSE MODEL OF ASTHMA ARE PRECEDED BY IMMUNE COMPLEX VASCULITIS AND INDUCED BRONCHIAL ASSOCIATED LYMPHOID TISSUE (iBALT)

    PubMed Central

    Guest, Ian; Sell, Stewart

    2015-01-01

    We systematically examined by immune-histology the lungs of some widely used mouse models of asthma. These models include sensitization by multiple intraperitoneal injections of soluble ovalbumin (OVA) or of OVA with alum, followed by three intranasal or aerosol challenges 3 days apart. Within 24 hours after a single challenge there is fibrinoid necrosis of arterial walls with deposition of immunoglobulin and OVA and infiltration of eosinophilic polymorphonuclear cells that lasts for about 3 days followed by peribronchial B-cell infiltration and slight reversible goblet cell hypertrophy. After 2 challenges, severe eosinophilic vasculitis is present at 6 hours, increases by 72 hours and then declines; B-cell proliferation and significant goblet cell hypertrophy and hyperplasia (GCHTH) and bronchial smooth muscle hypertrophy recur more prominently. After 3 challenges, there is significantly increased induced bronchus associated lymphoid tissue (iBALT) formation, GCHTH and smooth muscle hypertrophy. Elevated levels of Th2 cytokines: IL-4, IL-5 and IL-13, are present in bronchial lavage fluids. Sensitized mice have precipitating antibody and positive Arthus skin reactions but also develop significant levels IgE antibody to OVA but only 1 week after challenge. We conclude that the asthma like lung lesions induced in these models is preceded by immune complex mediated eosinophilic vasculitis and iBALT formation. There are elevations of Th2 cytokines that most likely produce bronchial lesions that resemble human asthma. However, it is unlikely that mast cell activated atopic mechanisms are responsible as we found only a few presumed mast cells by toluidine blue and metachromatic staining limited to the most proximal part of the main stem bronchus, and none in the remaining main stem bronchus or in the lung periphery. PMID:26006019

  3. Tertiary Lymphoid Organs in Cancer Tissues

    PubMed Central

    Hiraoka, Nobuyoshi; Ino, Yoshinori; Yamazaki-Itoh, Rie

    2016-01-01

    Tertiary lymphoid organs (TLOs) are induced postnatally in non-lymphoid tissues such as those affected by chronic infections, autoimmune diseases, and chronic allograft rejection, and also in cancer tissues. TLOs are thought to provide important lymphocytic functional environments for both cellular and humoral immunity, similar to lymph nodes or Peyer’s patches. TLOs have a structure similar to that of lymph nodes or Peyer’s patches, including T cell zones, B cell follicles, and high endothelial venules (HEV) without encapsulation. Here, we review recent advances in our knowledge of TLOs in human solid cancers, including their location, structure, methods of evaluation, and clinicopathological impact. We also discuss the formation and/or maintenance of TLOs in cancer tissues in association with the tumor immune microenvironment, cancer invasion, and the tissue structure of the cancer stroma. PMID:27446075

  4. Duct-associated lymphoid tissue (DALT) of minor salivary glands and mucosal immunity.

    PubMed Central

    Nair, P N; Schroeder, H E

    1986-01-01

    Minor salivary glands (MSG) play a substantial role in the secretory immunoglobulin A (sIgA)-mediated immunity of the oral cavity. There are two possibilities for the induction of this immunity: (i) an explicitly local antigenic stimulus, or (ii) a remote stimulus as part of the so-called 'common mucosal immune system'. This communication is an attempt to consolidate available evidence in support of both possibilities and to address the former in detail. Although there is strong circumstantial evidence supporting the feasibility of MSG functioning as a part of the common mucosal immune system, direct experimental evidence is yet to emerge. On the other hand, there is increasing structural and physiological evidence in support of MSG serving as a local immunological organ. The purely local response is attributed to the presence of MSG duct-associated lymphoid tissue (DALT), which is comparable to gut- or bronchial-associated lymphoid tissue (GALT or BALT) in origin, tissue organization and function. DALT is accessible to oral antigens by retrograde passage through MSG ducts. Repeated topical antigenic challenging via the oral mucosa may result in the appearance of interacinar plasma cells carrying specific homologous antibodies in MSG. Gut or enteric priming of the same antigen, by passing the oral mucosa by gastric intubation, need not evoke a remote immune response in MSG. Since DALT is more likely to occur in healthy, young growing individuals, who are less likely to undergo bioptic examination of MSG, it has not yet been documented in humans. The physiologically induced DALT is apt to be confused with focal accumulations of lymphoid tissue in pathologically altered MSG, as a consequence of local and some systemic autoimmune diseases. An attempt is made to demarcaate healthy and pathological MSG on the basis of currently available clinical, serological, immunological and genetic evidence. Images Figure 1 Figure 2 PMID:3512423

  5. [Morphological characteristics of the lymphoid tissues in the newborn children].

    PubMed

    Aminova, G G; Grigorenko, D E; Rusina, A K; Erofeeva, L M

    2000-01-01

    Quantitative and qualitative analysis and statistical processing of thymus, trachea, duodenum ileum, coecum and appendix in newborns demonstrated that by the moment of birth peripheral immunogenesis organs were not equally formed due to peculiarities of their function in postnatal ontogenesis. Lymphoid nodules were absent in tracheal mucosa and adjacent lymph nodes showed loss of lymphoid noules aswell. However intensive formation of lymphoid structures took place in the walls of the gut, especially large intestine. The appendix, lymphoid tissue of which was not, in fact, developed at all, made an exception.

  6. Morphology of mucosa-associated lymphoid tissue in odontocetes.

    PubMed

    Silva, Fernanda M O; Guimarães, Juliana P; Vergara-Parente, Jociery E; Carvalho, Vitor L; Carolina, Ana; Meirelles, O; Marmontel, Miriam; Oliveira, Bruno S S P; Santos, Silvanise M; Becegato, Estella Z; Evangelista, Janaina S A M; Miglino, Maria Angelica

    2016-09-01

    This study describes the mucosa-associated lymphoid tissue (MALT) in odontocetes from the Brazilian coast and freshwater systems. Seven species were evaluated and tissue samples were analyzed by light, scanning and transmission electron microscopy, and immunohistochemistry. Laryngeal tonsil was a palpable oval mass located in the larynx, composed of a lymphoepithelial complex. Dense collections of lymphocytes were found in the skin of male fetus and calf. Clusters of lymphoid tissue were found in the uterine cervix of a reproductively active juvenile female and along the pulmonary artery of an adult female. Lymphoid tissues associated with the gastrointestinal tract were characterized by diffusely arranged or organized lymphocytes. The anal tonsil was composed of an aggregate of lymphoid tissue occurring exclusively in the anal canal, being composed of squamous epithelium branches. MALT was present in different tissues and organic systems of cetaceans, providing constant protection against mucosal pathogens present in their environment.

  7. Dynamics of HIV infection in lymphoid tissue network.

    PubMed

    Nakaoka, Shinji; Iwami, Shingo; Sato, Kei

    2016-03-01

    Human immunodeficiency virus (HIV) is a fast replicating ribonucleic acid virus, which can easily mutate in order to escape the effects of drug administration. Hence, understanding the basic mechanisms underlying HIV persistence in the body is essential in the development of new therapies that could eradicate HIV infection. Lymphoid tissues are the primary sites of HIV infection. Despite the recent progress in real-time monitoring technology, HIV infection dynamics in a whole body is unknown. Mathematical modeling and simulations provide speculations on global behavior of HIV infection in the lymphatic system. We propose a new mathematical model that describes the spread of HIV infection throughout the lymphoid tissue network. In order to represent the volume difference between lymphoid tissues, we propose the proportionality of several kinetic parameters to the lymphoid tissues' volume distribution. Under this assumption, we perform extensive numerical computations in order to simulate the spread of HIV infection in the lymphoid tissue network. Numerical computations simulate single drug treatments of an HIV infection. One of the important biological speculations derived from this study is a drug saturation effect generated by lymphoid network connection. This implies that a portion of reservoir lymphoid tissues to which drug is not sufficiently delivered would inhibit HIV eradication despite of extensive drug injection.

  8. Tissue residency of innate lymphoid cells in lymphoid and nonlymphoid organs.

    PubMed

    Gasteiger, Georg; Fan, Xiying; Dikiy, Stanislav; Lee, Sue Y; Rudensky, Alexander Y

    2015-11-20

    Innate lymphoid cells (ILCs) contribute to barrier immunity, tissue homeostasis, and immune regulation at various anatomical sites throughout the body. How ILCs maintain their presence in lymphoid and peripheral tissues thus far has been unclear. We found that in the lymphoid and nonlymphoid organs of adult mice, ILCs are tissue-resident cells that were maintained and expanded locally under physiologic conditions, upon systemic perturbation of immune homeostasis and during acute helminth infection. However, at later time points after infection, cells from hematogenous sources helped to partially replenish the pool of resident ILCs. Thus, ILCs are maintained by self-renewal in broadly different microenvironments and physiological settings. Such an extreme "sedentary" lifestyle is consistent with the proposed roles of ILCs as sentinels and local keepers of tissue function. Copyright © 2015, American Association for the Advancement of Science.

  9. Quantitative Image Analysis of HIV-1 Infection in Lymphoid Tissue

    NASA Astrophysics Data System (ADS)

    Haase, Ashley T.; Henry, Keith; Zupancic, Mary; Sedgewick, Gerald; Faust, Russell A.; Melroe, Holly; Cavert, Winston; Gebhard, Kristin; Staskus, Katherine; Zhang, Zhi-Qiang; Dailey, Peter J.; Balfour, Henry H., Jr.; Erice, Alejo; Perelson, Alan S.

    1996-11-01

    Tracking human immunodeficiency virus-type 1 (HIV-1) infection at the cellular level in tissue reservoirs provides opportunities to better understand the pathogenesis of infection and to rationally design and monitor therapy A quantitative technique was developed to determine viral burden in two important cellular compartments in lymphoid tissues. Image analysis and in situ hybridization were combined to show that in the presymptomatic stages of infection there is a large, relatively stable pool of virions on the surfaces of follicular dendritic cells and a smaller pool of productively infected cells Despite evidence of constraints on HIV-1 replication in the infected cell population in lymphoid tissues, estimates of the numbers of these cells and the virus they could produce are consistent with the quantities of virus that have been detected in the bloodstream. The cellular sources of virus production and storage in lymphoid tissues can now be studied with this approach over the course of infection and treatment.

  10. Mucosa-associated lymphoid tissue in individuals with AIDS.

    PubMed

    Olegario, Janainna Grazielle Pacheco; Silva, Renata Calciolari Rossi e; Teixeira, Vicente de Paula Antunes; Castro, Eumênia Costa da Cunha; Corrêa, Rosana Rosa Miranda

    2011-06-01

    Vestibular folds (VF) protect upper airways, but contain fewer immune cells in AIDS patients, which affects the structure of lymphoid follicles (LF). To characterize fibrosis and immunoglobulin production in vestibular fold lymphoid tissues of AIDS patients with or with no infection and malnutrition. A retrospective study of 71 adult vestibular fold autopsy specimens. The morphological analysis was done using the picrosirius staining method. Immunohistochemical methods consisted of anti-IgA, anti IgG, and anti IgM antibodies. Fibrosis was less intense in AIDS patients compared to subjects without AIDS; the same applied to patients with infection or malnutrition. IgA and IgG titers were higher in AIDS patients; IgM titers were higher in cases with infection. This study helps understand variations in lymphoid follicle components of AIDS patients; it also shows the influence of architectural changes and the effect of associated respiratory infection and malnutrition on lymphoid follicle function.

  11. Mucosa associated lymphoid tissue lymphoma of lung: a case report.

    PubMed

    Gangopadhyay, Subir; Deb, Asit Ranjan; Aich, Ranen Karti; Chakraborty, Sudipto; Das, Diptimoy; Dee, Abhijit

    2010-07-01

    Mucosa associated lymphoid tissue lymphoma is a rare disease particularly when occurring in the lungs. In 1983, Issacson and Wright first described it as a distinct clinicopathological entity. A 39-year-old woman was suffering from mucosa associated lymphoid tissue lymphoma of the lung and was treated with moderate dose radiotherapy only. Six months after treatment the woman is symptom free and without any evidence of relapse. The disease undergoes a very indolent course and local form of treatment like surgery or radiotherapy is effective though radiotherapy is probably associated with higher local control rate and event free survival particularly in early stages. But for diagnostic purpose thoracotomy is generally required in pulmonary variety. Due to rarity of cases it is almost impossible to compare surgery with radiotherapy in mucosa associated lymphoid tissue lymphoma disorder in a prospective manner. Radiotherapy is the preferred mode of treatment either alone or in combination with surgery.

  12. Collaboration of epithelial cells with organized mucosal lymphoid tissues.

    PubMed

    Neutra, M R; Mantis, N J; Kraehenbuhl, J P

    2001-11-01

    Immune surveillance of mucosal surfaces requires the delivery of intact macromolecules and microorganisms across epithelial barriers to organized mucosal lymphoid tissues. Transport, processing and presentation of foreign antigens, as well as local induction and clonal expansion of antigen-specific effector lymphocytes, involves a close collaboration between organized lymphoid tissues and the specialized follicle-associated epithelium. M cells in the follicle-associated epithelium transport foreign macromolecules and microorganisms to antigen-presenting cells within and under the epithelial barrier. Determination of the earliest cellular interactions that occur in and under the follicle-associated epithelium could greatly facilitate the design of effective mucosal vaccines in the future.

  13. Quantitative image analysis of HIV-1 infection in lymphoid tissue

    SciTech Connect

    Haase, A.T.; Zupancic, M.; Cavert, W.

    1996-11-08

    Tracking human immunodeficiency virus-type 1 (HIV-1) infection at the cellular level in tissue reservoirs provides opportunities to better understand the pathogenesis of infection and to rationally design and monitor therapy. A quantitative technique was developed to determine viral burden in two important cellular compartments in lymphoid developed to determine viral burden in two important cellular compartments in lymphoid tissues. Image analysis and in situ hybridization were combined to show that in the presymptomatic stages of infection there is a large, relatively stable pool of virions on the surfaces of follicular dendritic cells and a smaller pool of productivity infected cells. Despite evidence of constraints on HIV-1 replication in the infected cell population in lymphoid tissues, estimates of the numbers of these cells and the virus they could produce are consistent with the quantities of virus that have been detected in the bloodstream. The cellular sources of virus production and storage in lymphoid tissues can now be studied with this approach over the course of infection and treatment. 22 refs., 2 figs., 2 tabs.

  14. Characterization of nasal cavity-associated lymphoid tissue in ducks.

    PubMed

    Kang, Haihong; Yan, Mengfei; Yu, Qinghua; Yang, Qian

    2014-05-01

    The nasal mucosa is involved in immune defense, as it is the first barrier for pathogens entering the body through the respiratory tract. The nasal cavity-associated lymphoid tissue (NALT), which is found in the mucosa of the nasal cavity, is considered to be the main mucosal immune inductive site in the upper respiratory tract. NALT has been found in humans and many mammals, which contributes to local and systemic immune responses after intranasal vaccination. However, there are very few data on NALT in avian species, especially waterfowl. For this study, histological sections of the nasal cavities of Cherry Valley ducks were used to examine the anatomical location and histological characteristics of NALT. The results showed that several lymphoid aggregates are present in the ventral wall of the nasal cavity near the choanal cleft, whereas several more lymphoid aggregates were located on both sides of the nasal septum. In addition, randomly distributed intraepithelial lymphocytes and isolated lymphoid follicles were observed in the regio respiratoria of the nasal cavity. There were also a few lymphoid aggregates located in the lamina propria of the regio vestibularis, which was covered with a stratified squamous epithelium. This study focused on the anatomic and histological characteristics of the nasal cavity of the duck and performed a systemic overview of NALT. This will be beneficial for further understanding of immune mechanisms after nasal vaccination and the development of effective nasal vaccines for waterfowls. Copyright © 2014 Wiley Periodicals, Inc.

  15. Human natural killer cell development in secondary lymphoid tissues

    PubMed Central

    Freud, Aharon G.; Yu, Jianhua; Caligiuri, Michael A.

    2014-01-01

    For nearly a decade it has been appreciated that critical steps in human natural killer (NK) cell development likely occur outside of the bone marrow and potentially necessitate distinct microenvironments within extramedullary tissues. The latter include the liver and gravid uterus as well as secondary lymphoid tissues such as tonsils and lymph nodes. For as yet unknown reasons these tissues are naturally enriched with NK cell developmental intermediates (NKDI) that span a maturation continuum starting from an oligopotent CD34+CD45RA+ hematopoietic precursor cell to a cytolytic mature NK cell. Indeed despite the detection of NKDI within the aforementioned tissues, relatively little is known about how, why, and when these tissues may be most suited to support NK cell maturation and how this process fits in with other components of the human immune system. With the discovery of other innate lymphoid subsets whose immunophenotypes overlap with those of NKDI, there is also need to revisit and potentially re-characterize the basic immunophenotypes of the stages of the human NK cell developmental pathway in vivo. In this review, we provide an overview of human NK cell development in secondary lymphoid tissues and discuss the many questions that remain to be answered in this exciting field. PMID:24661538

  16. Human natural killer cell development in secondary lymphoid tissues.

    PubMed

    Freud, Aharon G; Yu, Jianhua; Caligiuri, Michael A

    2014-04-01

    For nearly a decade it has been appreciated that critical steps in human natural killer (NK) cell development likely occur outside of the bone marrow and potentially necessitate distinct microenvironments within extramedullary tissues. The latter include the liver and gravid uterus as well as secondary lymphoid tissues such as tonsils and lymph nodes. For as yet unknown reasons these tissues are naturally enriched with NK cell developmental intermediates (NKDI) that span a maturation continuum starting from an oligopotent CD34(+)CD45RA(+) hematopoietic precursor cell to a cytolytic mature NK cell. Indeed despite the detection of NKDI within the aforementioned tissues, relatively little is known about how, why, and when these tissues may be most suited to support NK cell maturation and how this process fits in with other components of the human immune system. With the discovery of other innate lymphoid subsets whose immunophenotypes overlap with those of NKDI, there is also need to revisit and potentially re-characterize the basic immunophenotypes of the stages of the human NK cell developmental pathway in vivo. In this review, we provide an overview of human NK cell development in secondary lymphoid tissues and discuss the many questions that remain to be answered in this exciting field.

  17. Type 3 innate lymphoid cell depletion is mediated by TLRs in lymphoid tissues of simian immunodeficiency virus–infected macaques

    PubMed Central

    Xu, Huanbin; Wang, Xiaolei; Lackner, Andrew A.; Veazey, Ronald S.

    2015-01-01

    Innate lymphoid cells (ILCs) type 3, also known as lymphoid tissue inducer cells, plays a major role in both the development and remodeling of organized lymphoid tissues and the maintenance of adaptive immune responses. HIV/simian immunodeficiency virus (SIV) infection causes breakdown of intestinal barriers resulting in microbial translocation, leading to systemic immune activation and disease progression. However, the effects of HIV/SIV infection on ILC3 are unknown. Here, we analyzed ILC3 from mucosal and systemic lymphoid tissues in chronically SIV-infected macaques and uninfected controls. ILC3 cells were defined and identified in macaque lymphoid tissues as non-T, non-B (lineage-negative), c-Kit+IL-7Rα+ (CD117+CD127+) cells. These ILC3 cells highly expressed CD90 (∼63%) and aryl hydrocarbon receptor and produced IL-17 (∼63%), IL-22 (∼36%), and TNF-α (∼72%) but did not coexpress CD4 or NK cell markers. The intestinal ILC3 cell loss correlated with the reduction of total CD4+ T cells and T helper (Th)17 and Th22 cells in the gut during SIV infection (P < 0.001). Notably, ILC3 could be induced to undergo apoptosis by microbial products through the TLR2 (lipoteichoic acid) and/or TLR4 (LPS) pathway. These findings indicated that persistent microbial translocation may result in loss of ILC3 in lymphoid tissues in SIV-infected macaques, further contributing to the HIV-induced impairment of gut-associated lymphoid tissue structure and function, especially in mucosal tissues.—Xu, H., Wang, X., Lackner, A. A., Veazey, R. S. Type 3 innate lymphoid cell depletion is mediated by TLRs in lymphoid tissues of simian immunodeficiency virus–infected macaques. PMID:26283536

  18. Vitamin A Controls the Presence of RORγ+ Innate Lymphoid Cells and Lymphoid Tissue in the Small Intestine.

    PubMed

    Goverse, Gera; Labao-Almeida, Carlos; Ferreira, Manuela; Molenaar, Rosalie; Wahlen, Sigrid; Konijn, Tanja; Koning, Jasper; Veiga-Fernandes, Henrique; Mebius, Reina E

    2016-06-15

    Changes in diet and microbiota have determining effects on the function of the mucosal immune system. For example, the active metabolite of vitamin A, retinoic acid (RA), has been described to maintain homeostasis in the intestine by its influence on both lymphocytes and myeloid cells. Additionally, innate lymphoid cells (ILCs), important producers of cytokines necessary for intestinal homeostasis, are also influenced by vitamin A in the small intestines. In this study, we show a reduction of both NCR(-) and NCR(+) ILC3 subsets in the small intestine of mice raised on a vitamin A-deficient diet. Additionally, the percentages of IL-22-producing ILCs were reduced in the absence of dietary vitamin A. Conversely, mice receiving additional RA had a specific increase in the NCR(-) ILC3 subset, which contains the lymphoid tissue inducer cells. The dependence of lymphoid tissue inducer cells on vitamin A was furthermore illustrated by impaired development of enteric lymphoid tissues in vitamin A-deficient mice. These effects were a direct consequence of ILC-intrinsic RA signaling, because retinoic acid-related orphan receptor γt-Cre × RARα-DN mice had reduced numbers of NCR(-) and NCR(+) ILC3 subsets within the small intestine. However, lymphoid tissue inducer cells were not affected in these mice nor was the formation of enteric lymphoid tissue, demonstrating that the onset of RA signaling might take place before retinoic acid-related orphan receptor γt is expressed on lymphoid tissue inducer cells. Taken together, our data show an important role for vitamin A in controlling innate lymphoid cells and, consequently, postnatal formed lymphoid tissues within the small intestines. Copyright © 2016 by The American Association of Immunologists, Inc.

  19. Automatic Nervous System Distribution and Function in Lymphoid Tissues.

    DTIC Science & Technology

    1986-05-15

    thymus, thymic-related lymph nodes, the bone marrow, the spleen, gut associated lymphoid tissue (GALT) and the chick bursa of Fabricius, S. vrifyina...projections in the day-old chick indicates that the chick, like the mouse, receives vagal innervation during embryonic development (these neuronal centers...represent the source for vagal efferents in the chick ). The intrathymic distribution of these vagal cholinergic (AChE-positive) nerves in the chick

  20. Distribution of B lymphocyte subsets in normal lymphoid tissue.

    PubMed Central

    Murray, L J; Swerdlow, S H; Habeshaw, J A

    1984-01-01

    Using the ABC avidin-biotin peroxidase techniques and a series of monoclonal antibodies against B cell associated antigens, the anatomical distribution of B lymphocyte subsets was studied in reactive lymph node, tonsil and spleen. Evidence is presented for at least five major phenotypically distinct B cell subsets, each localized to specific compartments of peripheral lymphoid tissue. The possible relationship of these subsets of B lymphocytes to activation, maturation and function in the B cell lineage is discussed. Images Fig. 2 PMID:6375918

  1. Locations of gut-associated lymphoid tissue in the 3-month-old chicken: a review.

    PubMed

    Casteleyn, C; Doom, M; Lambrechts, E; Van den Broeck, W; Simoens, P; Cornillie, P

    2010-06-01

    The lymphoid tissue that is associated with the intestinal tract, the so-called gut-associated lymphoid tissue (GALT), is well developed in the chicken. Depending on the location, it is present as aggregations of lymphoid cells, or organized in lymphoid follicles and tonsils. From proximal to distal, the intestinal tract contains a pharyngeal tonsil, diffuse lymphoid tissue and lymphoid follicles in the cervical and thoracic parts of the oesophagus, an oesophageal tonsil, diffuse lymphoid tissue in the proventriculus, a pyloric tonsil, Peyer's patches, Meckel's diverticulum, two caecal tonsils, diffuse lymphoid tissue in the rectum, the bursa of Fabricius, and diffuse lymphoid tissue in the wall of the proctodeum. The lymphoid tissues are frequently covered by a lympho-epithelium that is infiltrated by lymphoid cells. Such an epithelium often contains M or microfold cells, which are specialized in antigen sampling and transport antigens to the underlying lymphoid tissue. A solid knowledge of the avian GALT could contribute to the development of vaccines to be administered orally. Additionally, immune stimulation via pre- and probiotics is based on the presence of a well-developed intestinal immune system.

  2. Migration and Tissue Tropism of Innate Lymphoid Cells

    PubMed Central

    Kim, Chang H.; Hashimoto-Hill, Seika; Kim, Myunghoo

    2016-01-01

    Innate lymphoid cell (ILCs) subsets differentially populate various barrier and non-barrier tissues, where they play important roles in tissue homeostasis and tissue-specific responses to pathogen attack. Recent findings have provided insight into the molecular mechanisms that guide ILC migration into peripheral tissues, revealing common features among different ILC subsets as well as important distinctions. Recent studies have also highlighted the impact of tissue-specific cues on ILC migration, and the importance of the local immunological milieu. We review these findings here and discuss how the migratory patterns and tissue tropism of different ILC subsets relate to the development and differentiation of these cells, and to ILC-mediated tissue-specific regulation of innate and adaptive immune responses. In this context we outline open questions and important areas of future research. PMID:26708278

  3. [Comparative study of lymphoid follicles in mucosa of pharynx and mucosal associated lymphoid tissues in paranasal sinuses].

    PubMed

    Zhai, Weigang; Yao, Min; Chen, Jue

    2013-08-01

    To study the relationship between the lymphoid follicles in mucous membrane of pharynx and mucosal associated lymphoid tissues (MALT). Ten folliculi obtained from 10 patients of follicular pharyngitis and mucosa taken form 10 patients of paranasal sinusitis were fixed in neutral formalin and embedded in paraffin. Sections were prepared, stained by H. E and by immunohistochemical method staining with S-100,and observe by light microscopy. We observed the morphology of lymphoid follicles in mucous membrane of pharynx with MALT in mucosa of paranasal sinusitis as the contrast. Lymphoid follicles in mucosa of pharynx compared with MALT in the mucosa of paranasal sinuses, there was no mantle zone, no typical germinal center and no mucosal epithelium, immunological staining with S-100 was week. The lymphoid follicles in mucosa of pharynx does not belong to the MALT.

  4. B cell repertoire expansion occurs in meningeal ectopic lymphoid tissue

    PubMed Central

    Lehmann-Horn, Klaus; Wang, Sheng-zhi; Sagan, Sharon A.; Zamvil, Scott S.

    2016-01-01

    Ectopic lymphoid tissues (ELT) can be found in multiple sclerosis (MS) and other organ-specific inflammatory conditions. Whether ELT in the meninges of central nervous system (CNS) autoimmune disease exhibit local germinal center (GC) activity remains unknown. In an experimental autoimmune encephalomyelitis model of CNS autoimmunity, we found activation-induced cytidine deaminase, a GC-defining enzyme, in meningeal ELT (mELT) densely populated by B and T cells. To determine GC activity in mELT, we excised meningeal lymphoid aggregates using laser capture microscopy and evaluated B cell repertoires in mELT and secondary lymphoid organs by next-generation immune repertoire sequencing. We found immunoglobulin heavy chain variable region sequences that were unique to mELT and had accumulated functionally relevant somatic mutations, together indicating localized antigen-driven affinity maturation. Our results suggest that B cells in mELT actively participate in CNS autoimmunity, which may be relevant to mELT in MS and ELT in other chronic inflammatory conditions. PMID:27942581

  5. Immunomodulation of gut-associated lymphoid tissue: current perspectives.

    PubMed

    Luongo, Diomira; D'Arienzo, Rossana; Bergamo, Paolo; Maurano, Francesco; Rossi, Mauro

    2009-01-01

    The gut-associated lymphoid tissue is deputed both to protect from infectious diseases and to evoke immune tolerance. Efficient responses need mucosal adjuvants: starting from cholera toxin, new variants of cholera toxin were developed depleted of toxicity. In addition, lipid colloidal particles, bacterial DNA, and probiotics have been experimented. Tolerance is currently induced by means of the B subunit of cholera toxin, whereas new strategies encompass the use of probiotics, expansion of regulatory T cells and blocking of paracellular entry of antigens. Finally, we report different approaches developed for celiac disease, an immune-mediated disease whose triggering antigen is known.

  6. Neuropilin-1 Is Expressed on Lymphoid Tissue Residing LTi-like Group 3 Innate Lymphoid Cells and Associated with Ectopic Lymphoid Aggregates.

    PubMed

    Shikhagaie, Medya Mara; Björklund, Åsa K; Mjösberg, Jenny; Erjefält, Jonas S; Cornelissen, Anne S; Ros, Xavier Romero; Bal, Suzanne M; Koning, Jasper J; Mebius, Reina E; Mori, Michiko; Bruchard, Melanie; Blom, Bianca; Spits, Hergen

    2017-02-14

    Here, we characterize a subset of ILC3s that express Neuropilin1 (NRP1) and are present in lymphoid tissues, but not in the peripheral blood or skin. NRP1(+) group 3 innate lymphoid cells (ILC3s) display in vitro lymphoid tissue inducer (LTi) activity. In agreement with this, NRP1(+) ILC3s are mainly located in proximity to high endothelial venules (HEVs) and express cell surface molecules involved in lymphocyte migration in secondary lymphoid tissues via HEVs. NRP1 was also expressed on mouse fetal LTi cells, indicating that NRP1 is a conserved marker for LTi cells. Human NRP1(+) ILC3s are primed cells because they express CD45RO and produce higher amounts of cytokines than NRP1(-) cells, which express CD45RA. The NRP1 ligand vascular endothelial growth factor A (VEGF-A) served as a chemotactic factor for NRP1(+) ILC3s. NRP1(+) ILC3s are present in lung tissues from smokers and patients with chronic obstructive pulmonary disease, suggesting a role in angiogenesis and/or the initiation of ectopic pulmonary lymphoid aggregates. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  7. Immunohistochemistry of the lymphoid tissues of the tammar wallaby, Macropus eugenii

    PubMed Central

    Old, Julie M; Deane, Elizabeth M

    2002-01-01

    The lymphoid tissues of the metatherian mammal, the adult tammar wallaby, Macropus eugenii, were investigated using immunohistochemical techniques. Five cross-reactive antibodies previously shown to recognize surface markers in marsupial tissues and five previously untested antibodies were used. The distribution of T-cells in the tissue beds of spleen, lymph node, thymus, gut-associated lymphoid tissue (GALT) and bronchus-associated lymphoid tissue (BALT) was documented using antibodies to CD3 and CD5. Similarly, B-cells were identified in the same tissues using anti-CD79b. Antibodies to CD8, CD31, CD79a and CD68 failed to recognize cells in these tissue beds. In general the pattern of cellular distribution identified using these antibodies was similar to that observed in other marsupial and eutherian lymphoid tissues. This study provides further information on the commonality of lymphoid tissue structure in the two major groups of extant mammals, metatherians and eutherians. PMID:12363276

  8. Innate lymphoid cells in tissue homeostasis and diseases.

    PubMed

    Ignacio, Aline; Breda, Cristiane Naffah Souza; Camara, Niels Olsen Saraiva

    2017-08-18

    Innate lymphoid cells (ILCs) are the most recently discovered family of innate immune cells. They are a part of the innate immune system, but develop from the lymphoid lineage. They lack pattern-recognition receptors and rearranged receptors, and therefore cannot directly mediate antigen specific responses. The progenitors specifically associated with the ILCs lineage have been uncovered, enabling the distinction between ILCs and natural killer cells. Based on the requirement of specific transcription factors and their patterns of cytokine production, ILCs are categorized into three subsets (ILC1, ILC2 and ILC3). First observed in mucosal surfaces, these cell populations interact with hematopoietic and non-hematopoietic cells throughout the body during homeostasis and diseases, promoting immunity, commensal microbiota tolerance, tissue repair and inflammation. Over the last 8 years, ILCs came into the spotlight as an essential cell type able to integrate diverse host immune responses. Recently, it became known that ILC subsets play a key role in immune responses at barrier surfaces, interacting with the microbiota, nutrients and metabolites. Since the liver receives the venous blood directly from the intestinal vein, the intestine and liver are essential to maintain tolerance and can rapidly respond to infections or tissue damage. Therefore, in this review, we discuss recent findings regarding ILC functions in homeostasis and disease, with a focus on the intestine and liver.

  9. Innate lymphoid cells in tissue homeostasis and diseases

    PubMed Central

    Ignacio, Aline; Breda, Cristiane Naffah Souza; Camara, Niels Olsen Saraiva

    2017-01-01

    Innate lymphoid cells (ILCs) are the most recently discovered family of innate immune cells. They are a part of the innate immune system, but develop from the lymphoid lineage. They lack pattern-recognition receptors and rearranged receptors, and therefore cannot directly mediate antigen specific responses. The progenitors specifically associated with the ILCs lineage have been uncovered, enabling the distinction between ILCs and natural killer cells. Based on the requirement of specific transcription factors and their patterns of cytokine production, ILCs are categorized into three subsets (ILC1, ILC2 and ILC3). First observed in mucosal surfaces, these cell populations interact with hematopoietic and non-hematopoietic cells throughout the body during homeostasis and diseases, promoting immunity, commensal microbiota tolerance, tissue repair and inflammation. Over the last 8 years, ILCs came into the spotlight as an essential cell type able to integrate diverse host immune responses. Recently, it became known that ILC subsets play a key role in immune responses at barrier surfaces, interacting with the microbiota, nutrients and metabolites. Since the liver receives the venous blood directly from the intestinal vein, the intestine and liver are essential to maintain tolerance and can rapidly respond to infections or tissue damage. Therefore, in this review, we discuss recent findings regarding ILC functions in homeostasis and disease, with a focus on the intestine and liver. PMID:28878863

  10. Pulmonary mucosa-associated lymphoid tissue lymphoma revisited.

    PubMed

    Borie, Raphael; Wislez, Marie; Antoine, Martine; Copie-Bergman, Christiane; Thieblemont, Catherine; Cadranel, Jacques

    2016-04-01

    This general review sought to clarify the pathophysiological, diagnostic, prognostic, and therapeutic features of pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma.MALT lymphoma is the most common pulmonary B-cell lymphoma, which usually occurs in the context of acquired MALT. The disease is slow-growing with an asymptomatic chronic alveolar opacity visible on radiography. Diagnosis requires tissue samples that should be retrieved using minimally invasive techniques, such as bronchoscopy or computed tomography-guided biopsies. The pathophysiology includes cytogenetic abnormalities and autoimmune diseases, whereas an association with a chronic pulmonary infection is still suspected but not yet demonstrated. Disease prognosis is typically excellent and the current available treatments are discussed in this review, including the decision not to treat, surgery, and single- or double-agent chemotherapy. Copyright ©ERS 2016.

  11. Multispectral imaging fluorescence microscopy for lymphoid tissue analysis

    NASA Astrophysics Data System (ADS)

    Monici, Monica; Agati, Giovanni; Fusi, Franco; Mazzinghi, Piero; Romano, Salvatore; Pratesi, Riccardo; Alterini, Renato; Bernabei, Pietro A.; Rigacci, Luigi

    1999-01-01

    Multispectral imaging autofluorescence microscopy (MIAM) is used here for the analysis of lymphatic tissues. Lymph node biopsies, from patients with lympthoadenopathy of different origin have been examined. Natural fluorescence (NF) images of 3 micrometers sections were obtained using three filters peaked at 450, 550 and 680 nm with 50 nm bandpass. Monochrome images were combined together in a single RGB image. NF images of lymph node tissue sections show intense blue-green fluorescence of the connective stroma. Normal tissue shows follicles with faintly fluorescent lymphocytes, as expected fro the morphologic and functional characteristics of these cells. Other more fluorescent cells (e.g., plasma cells and macrophages) are evidenced. Intense green fluorescence if localized in the inner wall of the vessels. Tissues coming from patients affected by Hodgkin's lymphoma show spread fluorescence due to connective infiltration and no evidence of follicle organization. Brightly fluorescent large cells, presumably Hodgkin cells, are also observed. These results indicate that MIAM can discriminate between normal and pathological tissues on the basis of their natural fluorescence pattern, and, therefore, represent a potentially useful technique for diagnostic applications. Analysis of the fluorescence spectra of both normal and malignant lymphoid tissues resulted much less discriminatory than MIAM.

  12. Colonic mucosa-associated lymphoid tissue lymphoma identified by chromoendoscopy

    PubMed Central

    Seo, Sang-Wook; Lee, Seung-Hwa; Lee, Duck-Joo; Kim, Kwang-Min; Kang, Joon-Koo; Kim, Do-Wan; Lee, Jeong-Hun

    2014-01-01

    Colonic mucosa-associated lymphoid tissue (MALT) lymphomas are a rare occurrence and the definitive treatment has not been established. Solitary or multiple, elevated or polypoid lesions are the usual appearances of MALT lymphoma in the large intestine and sometimes the surface may reveal abnormal vascularity. Herein, we report a case of MALT lymphoma and review the relevant literature. Upon colonoscopy, a suspected pathologic lesion was observed in the proximal transverse colon. The lesion could be distinguished more prominently after using narrow-band imaging mode and indigo carmine-dye spraying chromoendoscopy. Histopathologic examination of this biopsy specimen revealed lymphoepithelial lesions with diffuse proliferation of atypical lymphoid cells effacing the glandular architecture and centrocyte-like cells infiltrating the lamina propria. Immunohistochemical analyses showed that tumor cells were positive for CD20 and Bcl-2e, and negative for CD10, CD23, and Bcl-6. According to Ann-Arbor staging system, the patient had stage IIE. A partial colectomy with dissection of the paracolic lymph nodes was performed. Until now, there is no recurrence of lymphoma at follow-up. PMID:25561821

  13. Colonization and effector functions of innate lymphoid cells in mucosal tissues

    PubMed Central

    Kim, Myunghoo; Kim, Chang H.

    2016-01-01

    Innate lymphoid cells (ILCs) protect mucosal barrier tissues to fight infection and maintain tissue integrity. ILCs and their progenitors are developmentally programmed to migrate, differentiate and populate various mucosal tissues and associated lymphoid tissues. Functionally mature ILC subsets respond to diverse pathogens such as bacteria, viruses, fungi and parasites in subset-specific manners. In this review, we will discuss how ILCs populate mucosal tissues and regulate immune responses to distinct pathogens to protect the host and maintain tissue integrity. PMID:27365193

  14. Defining HIV and SIV Reservoirs in Lymphoid Tissues

    PubMed Central

    Deleage, Claire; Wietgrefe, Stephen W.; Del Prete, Gregory; Morcock, David R.; Hao, Xing Pei; Piatak, Michael; Bess, Julian; Anderson, Jodi L.; Perkey, Katherine E.; Reilly, Cavan; McCune, Joseph M.; Haase, Ashley T.; Lifson, Jeffrey D.; Schacker, Timothy W.; Estes, Jacob D.

    2016-01-01

    A primary obstacle to an HIV-1 cure is long-lived viral reservoirs, which must be eliminated or greatly reduced. Cure strategies have largely focused on monitoring changes in T cell reservoirs in peripheral blood (PB), even though the lymphoid tissues (LT) are primary sites for viral persistence. To track and discriminate viral reservoirs within tissue compartments we developed a specific and sensitive next-generation in situ hybridization approach to detect vRNA, including vRNA+ cells and viral particles (“RNAscope”), vDNA+ cells (“DNAscope”) and combined vRNA and vDNA with immunohistochemistry to detect and phenotype active and latently infected cells in the same tissue section. RNAscope is highly sensitive with greater speed of analysis compared to traditional in situ hybridization. The highly sensitive and specific DNAscope detected SIV/HIV vDNA+ cells, including duplexed detection of vDNA and vRNA or immunophenotypic markers in the same section. Analysis of LT samples from macaques prior to and during combination antiretroviral therapy demonstrated that B cell follicles are an important anatomical compartment for both latent and active viral persistence during treatment. These new tools should allow new insights into viral reservoir biology and evaluation of cure strategies. PMID:27430032

  15. Defining HIV and SIV Reservoirs in Lymphoid Tissues.

    PubMed

    Deleage, Claire; Wietgrefe, Stephen W; Del Prete, Gregory; Morcock, David R; Hao, Xing Pei; Piatak, Michael; Bess, Julian; Anderson, Jodi L; Perkey, Katherine E; Reilly, Cavan; McCune, Joseph M; Haase, Ashley T; Lifson, Jeffrey D; Schacker, Timothy W; Estes, Jacob D

    2016-01-01

    A primary obstacle to an HIV-1 cure is long-lived viral reservoirs, which must be eliminated or greatly reduced. Cure strategies have largely focused on monitoring changes in T cell reservoirs in peripheral blood (PB), even though the lymphoid tissues (LT) are primary sites for viral persistence. To track and discriminate viral reservoirs within tissue compartments we developed a specific and sensitive next-generation in situ hybridization approach to detect vRNA, including vRNA+ cells and viral particles ("RNAscope"), vDNA+ cells ("DNAscope") and combined vRNA and vDNA with immunohistochemistry to detect and phenotype active and latently infected cells in the same tissue section. RNAscope is highly sensitive with greater speed of analysis compared to traditional in situ hybridization. The highly sensitive and specific DNAscope detected SIV/HIV vDNA+ cells, including duplexed detection of vDNA and vRNA or immunophenotypic markers in the same section. Analysis of LT samples from macaques prior to and during combination antiretroviral therapy demonstrated that B cell follicles are an important anatomical compartment for both latent and active viral persistence during treatment. These new tools should allow new insights into viral reservoir biology and evaluation of cure strategies.

  16. Tissue-specific effector functions of innate lymphoid cells

    PubMed Central

    Björkström, Niklas K; Kekäläinen, Eliisa; Mjösberg, Jenny

    2013-01-01

    Innate lymphoid cells (ILCs) is the collective term for a group of related innate lymphocytes, including natural killer (NK) cells and the more recently discovered non-NK ILCs, which all lack rearranged antigen receptors such as those expressed by T and B cells. Similar to NK cells, the newly discovered ILCs depend on the transcription factor Id2 and the common γ-chain of the interleukin-2 receptor for development. However, in contrast to NK cells, non-NK ILCs also require interleukin-7. In addition to the cytotoxic functions of NK cells, assuring protection against tumour development and viruses, new data indicate that ILCs contribute to a wide range of homeostatic and pathophysiological conditions in various organs via specialized cytokine production capabilities. Here we summarize current knowledge on ILCs with a particular emphasis on their tissue-specific effector functions, in the gut, liver, lungs and uterus. When possible, we try to highlight the role that these cells play in humans. PMID:23489335

  17. The development and function of mucosal lymphoid tissues: a balancing act with micro-organisms.

    PubMed

    Randall, T D; Mebius, R E

    2014-05-01

    Mucosal surfaces are constantly exposed to environmental antigens, colonized by commensal organisms and used by pathogens as points of entry. As a result, the immune system has devoted the bulk of its resources to mucosal sites to maintain symbiosis with commensal organisms, prevent pathogen entry, and avoid unnecessary inflammatory responses to innocuous antigens. These functions are facilitated by a variety of mucosal lymphoid organs that develop during embryogenesis in the absence of microbial stimulation as well as ectopic lymphoid tissues that develop in adults following microbial exposure or inflammation. Each of these lymphoid organs samples antigens from different mucosal sites and contributes to immune homeostasis, commensal containment, and immunity to pathogens. Here we discuss the mechanisms, mostly based on mouse studies, that control the development of mucosal lymphoid organs and how the various lymphoid tissues cooperate to maintain the integrity of the mucosal barrier.

  18. Lymphoid tissue inducer cells: architects of CD4 immune responses in mice and men.

    PubMed

    Kim, M-Y; Kim, K-S; McConnell, F; Lane, P

    2009-07-01

    In this review, we summarize the current understanding of the multiple functions of the mouse lymphoid tissue inducer (LTi) cells in: (i) the development of organized lymphoid tissue, (ii) the generation and maintenance of CD4-dependent immunity in adult lymphoid tissues; and (iii) the regulation of central tolerance in thymus. By contrast with mouse LTi cells, which have been well described, the human equivalent is only just beginning to be characterized. Human LTi-like cells expressing interleukin (IL)-22 have been identified recently and found to differentiate into natural killer (NK) cells. The relationship of LTi cells to NK cells is discussed in the light of several studies reporting a close relationship in the mouse between LTi cells and transcription factor retinoid-related orphan receptor gammat-dependent IL-22 producing NK cells in the gut. We also outline our data suggesting that these cells are present in adult human lymphoid tissues.

  19. Interleukin-22-producing natural killer cells and lymphoid tissue inducer-like cells in mucosal immunity.

    PubMed

    Colonna, Marco

    2009-07-17

    Blood, lymphoid tissues, and placenta contain diverse subpopulations of natural killer (NK) cells that possess distinct immune functions. Recent studies have shown that human and mouse gut-associated lymphoid tissues harbor a unique NK cell subset that specializes in production of interleukin (IL)-22. This cytokine plays a role in host defense of mucosal barriers, although dysregulated secretion may cause autoimmune disease. In parallel, human fetal lymphoid tissue inducer (LTi) cells and mouse adult LTi-like cells in secondary lymphoid tissues were found to release IL-22, as well as IL-17, a proinflammatory cytokine that mediates host defense against extracellular pathogens. Here, we compare these recently identified immune cells, reviewing what is known about their anatomical location, differentiation requirements, function, and potential involvement in host defense and autoimmunity. Finally, we discuss the challenges faced in furthering our understanding of the developmental relationships and role of NK and LTi-like cells in mucosal immune responses.

  20. Colonization and effector functions of innate lymphoid cells in mucosal tissues.

    PubMed

    Kim, Myunghoo; Kim, Chang H

    2016-10-01

    Innate lymphoid cells (ILCs) protect mucosal barrier tissues to fight infection and maintain tissue integrity. ILCs and their progenitors are developmentally programmed to migrate, differentiate and populate various mucosal tissues and associated lymphoid tissues. Functionally mature ILC subsets respond to diverse pathogens such as bacteria, viruses, fungi and parasites in subset-specific manners. In this review, we will discuss how ILCs populate mucosal tissues and regulate immune responses to distinct pathogens to protect the host and maintain tissue integrity. Copyright © 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  1. Scrapie-Specific Pathology of Sheep Lymphoid Tissues

    PubMed Central

    McGovern, Gillian; Jeffrey, Martin

    2007-01-01

    Transmissible spongiform encephalopathies (TSEs) or prion diseases often result in accumulation of disease-associated PrP (PrPd) in the lymphoreticular system (LRS), specifically in association with follicular dendritic cells (FDCs) and tingible body macrophages (TBMs) of secondary follicles. We studied the effects of sheep scrapie on lymphoid tissue in tonsils and lymph nodes by light and electron microscopy. FDCs of sheep were grouped according to morphology as immature, mature or regressing. Scrapie was associated with FDC dendrite hypertrophy and electron dense deposit or vesicles. PrPd was located using immunogold labelling at the plasmalemma of FDC dendrites and, infrequently, mature B cells. Abnormal electron dense deposits surrounding FDC dendrites were identified as immunoglobulins suggesting that excess immune complexes are retained and are indicative of an FDC dysfunction. Within scrapie-affected lymph nodes, macrophages outside the follicle and a proportion of germinal centre TBMs accumulated PrPd within endosomes and lysosomes. In addition, TBMs showed PrPd in association with the cell membrane, non-coated pits and vesicles, and also with discrete, large and random endoplasmic reticulum networks, which co-localised with ubiquitin. These observations suggest that PrPd is internalised via the caveolin-mediated pathway, and causes an abnormal disease-related alteration in endoplasmic reticulum structure. In contrast to current dogma, this study shows that sheep scrapie is associated with cytopathology of germinal centres, which we attribute to abnormal antigen complex trapping by FDCs and abnormal endocytic events in TBMs. The nature of the sub-cellular changes in FDCs and TBMs differs from those of scrapie infected neurones and glial cells suggesting that different PrPd/cell membrane interactions occur in different cell types. PMID:18074028

  2. Primary esophageal mucosa-associated lymphoid tissue lymphoma

    PubMed Central

    Ma, Qiang; Zhang, Chun; Fang, San’gao; Zhong, Peng; Zhu, Xiangfeng; Lin, Li; Xiao, Hualiang

    2017-01-01

    Abstract Rationale: Mucosa-associated lymphoid tissue (MALT) lymphoma is a low grade malignant B cell lymphoma which occurs mainly in the organs having mucosal layer. Though gastrointestinal tract is the most commonly involved extranodal site, primary esophageal MALT lymphoma is very rare with less than 20 cases reported in literature. Patient concerns: A 75-year-old man was referred to our hospital for evaluation of dysphagia. Endoscopy revealed a submucosal tumor located in the middle and lower third of esophagus. CT chest and endoscopic ultrasound revealed a 15.5 × 5.9 × 4.0 cm well circumscribed submucosa esophageal tumor. Test for serum antibody against H. pylori was negative. Due to the large tumor size, patient underwent surgical resection. Histological examination showed a submucosal tumor consisting of multiple nodules of varying sizes with intact covering squamous epithelium. The nodules were mainly composed of diffusely and monoclonal proliferating centrocyte-like or monocyte-like cells. Follicular colonizations were observed without lymphoepithelial lesions. The tumor cells were diffusely positive for CD20, PAX-5, Bcl-2 and follicular dendritic cells were positive for CD21, CD23. Monoclonal gene rearrangement was positive for immunoglobulin heavy chain gene, Kappa light chain gene and Lambda light chain gene. Diagnoses: Based on these findings, final diagnosis of esophageal MALT lymphoma was made. Outcomes: At 8 month follow up, no recurrence or metastases was detected. Lessons: Esophageal MALT lymphoma is a rare disease with definitive diagnosis possible only after histopathological examination. It carries good prognosis due to low malignant potential. PMID:28353588

  3. Enzyme histochemistry of cecal lymphoid tissue during prenatal period of buffalo

    PubMed Central

    Kapoor, Kritima; Singh, Opinder

    2016-01-01

    Aim: This study was designed to elucidate the histoenzymic distribution of enzymes, i.e., phosphatases, oxidoreductases, dehydrogenases, and diaphorases in cecal lymphoid tissue during its development in the prenatal period. Materials and Methods: The study was conducted on cecum of 15 buffalo fetuses ranging from 16 cm curved crown-rump length (CVRL) (100 days) to 100 cm CVRL (full term). The fetuses were categorized into three groups based on their CVRL. Results: In Group I, the distribution of enzymes was uniformly weak in developing villi-like projections in cecum and completely absent from submucosa. In Group II, the enzymes showed a moderate to strong activity in epithelium lining tunica mucosa which progressively decreased as the fetus progresses toward late gestational age. However, the intense activity of enzymes was observed in developing lymphoid tissue in this group. In Group III, distribution of enzymes reduced in tunica mucosa of cecum with advancing age, whereas the intense activity was noticed in the developed lymphoid tissue complex. Conclusion: The distribution of enzymes was completely absent from submucosal region in cecum of Group I as there was no lymphoid tissue development at this age. In Group II, the enzymes showed a moderate to strong activity in epithelium lining tunica mucosa which progressively decreased toward late gestational age but an intense activity was observed in developing lymphoid tissue. In Group III, distribution of enzymes reduced in tunica mucosa with advancing age with intense activity noticed in the developed lymphoid tissue complex. PMID:27733804

  4. Lymphocyte trafficking and HIV infection of human lymphoid tissue in a rotating wall vessel bioreactor

    NASA Technical Reports Server (NTRS)

    Margolis, L. B.; Fitzgerald, W.; Glushakova, S.; Hatfill, S.; Amichay, N.; Baibakov, B.; Zimmerberg, J.

    1997-01-01

    The pathogenesis of HIV infection involves a complex interplay between both the infected and noninfected cells of human lymphoid tissue, the release of free viral particles, the de novo infection of cells, and the recirculatory trafficking of peripheral blood lymphocytes. To develop an in vitro model for studying these various aspects of HIV pathogenesis we have utilized blocks of surgically excised human tonsils and a rotating wall vessel (RWV) cell culture system. Here we show that (1) fragments of the surgically excised human lymphoid tissue remain viable and retain their gross cytoarchitecture for at least 3 weeks when cultured in the RWV system; (2) such lymphoid tissue gradually shows a loss of both T and B cells to the surrounding growth medium; however, this cellular migration is reversible as demonstrated by repopulation of the tissue by labeled cells from the growth medium; (3) this cellular migration may be partially or completely inhibited by embedding the blocks of lymphoid tissue in either a collagen or agarose gel matrix; these embedded tissue blocks retain most of the basic elements of a normal lymphoid cytoarchitecture; and (4) both embedded and nonembedded RWV-cultured blocks of human lymphoid tissue are capable of productive infection by HIV-1 of at least three various strains of different tropism and phenotype, as shown by an increase in both p24 antigen levels and free virus in the culture medium, and by the demonstration of HIV-1 RNA-positive cells inside the tissue identified by in situ hybridization. It is therefore reasonable to suggest that gel-embedded and nonembedded blocks of human lymphoid tissue, cocultured with a suspension of tonsillar lymphocytes in an RWV culture system, constitute a useful model for simulating normal lymphocyte recirculatory traffic and provide a new tool for testing the various aspects of HIV pathogenesis.

  5. Lymphocyte trafficking and HIV infection of human lymphoid tissue in a rotating wall vessel bioreactor

    NASA Technical Reports Server (NTRS)

    Margolis, L. B.; Fitzgerald, W.; Glushakova, S.; Hatfill, S.; Amichay, N.; Baibakov, B.; Zimmerberg, J.

    1997-01-01

    The pathogenesis of HIV infection involves a complex interplay between both the infected and noninfected cells of human lymphoid tissue, the release of free viral particles, the de novo infection of cells, and the recirculatory trafficking of peripheral blood lymphocytes. To develop an in vitro model for studying these various aspects of HIV pathogenesis we have utilized blocks of surgically excised human tonsils and a rotating wall vessel (RWV) cell culture system. Here we show that (1) fragments of the surgically excised human lymphoid tissue remain viable and retain their gross cytoarchitecture for at least 3 weeks when cultured in the RWV system; (2) such lymphoid tissue gradually shows a loss of both T and B cells to the surrounding growth medium; however, this cellular migration is reversible as demonstrated by repopulation of the tissue by labeled cells from the growth medium; (3) this cellular migration may be partially or completely inhibited by embedding the blocks of lymphoid tissue in either a collagen or agarose gel matrix; these embedded tissue blocks retain most of the basic elements of a normal lymphoid cytoarchitecture; and (4) both embedded and nonembedded RWV-cultured blocks of human lymphoid tissue are capable of productive infection by HIV-1 of at least three various strains of different tropism and phenotype, as shown by an increase in both p24 antigen levels and free virus in the culture medium, and by the demonstration of HIV-1 RNA-positive cells inside the tissue identified by in situ hybridization. It is therefore reasonable to suggest that gel-embedded and nonembedded blocks of human lymphoid tissue, cocultured with a suspension of tonsillar lymphocytes in an RWV culture system, constitute a useful model for simulating normal lymphocyte recirculatory traffic and provide a new tool for testing the various aspects of HIV pathogenesis.

  6. Solitary Intestinal Lymphoid Tissue Provides a Productive Port of Entry for Salmonella enterica Serovar Typhimurium▿

    PubMed Central

    Halle, Stephan; Bumann, Dirk; Herbrand, Heike; Willer, Yvonne; Dähne, Sabrina; Förster, Reinhold; Pabst, Oliver

    2007-01-01

    Oral infection of mice with Salmonella enterica serovar Typhimurium results in the colonization of Peyer's patches, triggering a vigorous inflammatory response and immunopathology at these sites. Here we demonstrate that in parallel to Peyer's patches a strong inflammatory response occurs in the intestine, resulting in the appearance of numerous inflammatory foci in the intestinal mucosa. These foci surround small lymphoid cell clusters termed solitary intestinal lymphoid tissue (SILT). Salmonella can be observed inside SILT at early stages of infection, and the number of infected structures matches the number of inflammatory foci arising at later time points. Infection leads to enlargement and morphological destruction of SILT but does not trigger de novo formation of lymphoid tissue. In conclusion, SILT, a lymphoid compartment mostly neglected in earlier studies, represents a major site for Salmonella invasion and ensuing mucosal pathology. PMID:17283101

  7. Secondary Lymphoid Tissue Chemokine as an Immunotherapeutic Against Primary and Metastatic Breast Cancer

    DTIC Science & Technology

    2006-05-01

    CCR7 , which binds the chemokine secondary lymphoid chemokine (SLC, also called CCL21). In Task 1, we examined the effect of SLC/CCL21 administered via...express a common receptor, CCR7 , which binds secondary lymphoid tissue chemokine (SLC, also known as CCL21). Expression of CCR7 allows these cells to...for characterization and quantification of tumor- infiltrating DCs, T cells, and NK cells. Mice that received the experimental and control

  8. Secondary Lymphoid Tissue Chemokine as an Immunotherapeutic Against Primary and Metastatic Breast Cancer

    DTIC Science & Technology

    2005-05-01

    common receptor, CCR7 , which binds the chemokine SLC/CCL21. SLC/CCL21 is normally expressed in the lymphoid organs and coordinates the interactions...dendritic cells (DCs). T cells and DCs, as well as natural killer (NK) cells (which also have anti-tumor activity), express a common receptor, CCR7 , which...binds secondary lymphoid tissue chemokine (SLC, also known as CCL21). Expression of CCR7 allows these cells to migrate along gradients of this chemokine

  9. Vagal innervation is required for the formation of tertiary lymphoid tissue in colitis.

    PubMed

    Olivier, Brenda J; Cailotto, Cathy; van der Vliet, Jan; Knippenberg, Marlene; Greuter, Mascha J; Hilbers, Francisca W; Konijn, Tanja; Te Velde, Anje A; Nolte, Martijn A; Boeckxstaens, Guy E; de Jonge, Wouter J; Mebius, Reina E

    2016-10-01

    Tertiary lymphoid tissue (TLT) is lymphoid tissue that forms in adult life as a result of chronic inflammation in a tissue or organ. TLT has been shown to form in a variety of chronic inflammatory diseases, though it is not clear if and how TLT develops in the inflamed colon during inflammatory bowel disease. Here, we show that TLT develops as newly formed lymphoid tissue in the colon following dextran sulphate sodium induced colitis in C57BL/6 mice, where it can be distinguished from the preexisting colonic patches and solitary intestinal lymphoid tissue. TLT in the inflamed colon develops following the expression of lymphoid tissue-inducing chemokines and adhesion molecules, such as CXCL13 and VCAM-1, respectively, which are produced by stromal organizer cells. Surprisingly, this process of TLT formation was independent of the lymphotoxin signaling pathway, but rather under neuronal control, as we demonstrate that selective surgical ablation of vagus nerve innervation inhibits CXCL13 expression and abrogates TLT formation without affecting colitis. Sympathetic neuron denervation does not affect TLT formation. Hence, we reveal that inflammation in the colon induces the formation of TLT, which is controlled by innervation through the vagus nerve.

  10. Role of lymphotoxin and homeostatic chemokines in the development and function of local lymphoid tissues in the respiratory tract.

    PubMed

    Rangel-Moreno, Javier; Carragher, Damian; Randall, Troy D

    2007-01-01

    Secondary lymphoid organs are strategically placed to recruit locally activated antigen presenting cells (APCs) as well as naïve, recirculating T and B cells. The structure of secondary lymphoid organs - separated B and T zones, populations of specialized stromal cells, high endothelial venules and lymphatic vessles - has also evolved to maximize encounters between APCs and lymphocytes and to facilitate the expansion and differentiation of antigen-stimulated T and B cells. Many of the general mechanisms that govern the development and organization of secondary lymphoid organs have been identified over the last decade. However, the specific cellular and molecular interactions involved in the development and organization of each secondary lymphoid organ are slightly different and probably reflect the cell types available at that time and location. Here we review the mechanisms involved in the development, organization and function of local lymphoid tissues in the respiratory tract, including Nasal Associated Lymphoid Tissue (NALT) and inducible Bronchus Associated Lymphoid Tissue (iBALT).

  11. Peripheral Tissue Homing Receptor Control of Naïve, Effector, and Memory CD8 T Cell Localization in Lymphoid and Non-Lymphoid Tissues

    PubMed Central

    Brinkman, C. Colin; Peske, J. David; Engelhard, Victor Henry

    2013-01-01

    T cell activation induces homing receptors that bind ligands on peripheral tissue vasculature, programing movement to sites of infection and injury. There are three major types of CD8 effector T cells based on homing receptor expression, which arise in distinct lymphoid organs. Recent publications indicate that naïve, effector, and memory T cell migration is more complex than once thought; while many effectors enter peripheral tissues, some re-enter lymph nodes (LN), and contain central memory precursors. LN re-entry can depend on CD62L or peripheral tissue homing receptors. Memory T cells in LN tend to express the same homing receptors as their forebears, but often are CD62Lneg. Homing receptors also control CD8 T cell tumor entry. Tumor vasculature has low levels of many peripheral tissue homing receptor ligands, but portions of it resemble high endothelial venules (HEV), enabling naïve T cell entry, activation, and subsequent effector activity. This vasculature is associated with positive prognoses in humans, suggesting it may sustain ongoing anti-tumor responses. These findings reveal new roles for homing receptors expressed by naïve, effector, and memory CD8 T cells in controlling entry into lymphoid and non-lymphoid tissues. PMID:23966998

  12. Regression of gastric lymphoma of mucosa-associated lymphoid tissue with antibiotic therapy for Helicobacter pylori.

    PubMed

    Weber, D M; Dimopoulos, M A; Anandu, D P; Pugh, W C; Steinbach, G

    1994-12-01

    Regression of low-grade B cell gastric lymphoma of mucosa-associated lymphoid tissue after eradication of Helicobacter pylori with antibiotic therapy was recently shown in a small number of patients with low-volume tumors. A patient with a > 10 cm nodular gastric mucosa-associated lymphoid tissue lymphoma that caused hematemesis and weight loss is described. Antibiotic therapy of H. pylori resulted in full clinical recovery and resolution of the mass lesion and morphological features of lymphoma on routine histological examination. However, monotypic immunostaining of plasma cells persisted in a separate and grossly normal-appearing region of the stomach. Antibiotic therapy may be of benefit in patients with mucosa-associated lymphoid tissue lymphoma with mass lesions and significant signs and symptoms, but periodic search for residual lymphoma is needed.

  13. Establishment and function of tissue-resident innate lymphoid cells in the skin.

    PubMed

    Yang, Jie; Zhao, Luming; Xu, Ming; Xiong, Na

    2017-07-01

    Innate lymphoid cells (ILCs) are a newly classified family of immune cells of the lymphoid lineage. While they could be found in both lymphoid organs and non-lymphoid tissues, ILCs are preferentially enriched in barrier tissues such as the skin, intestine, and lung where they could play important roles in maintenance of tissue integrity and function and protection against assaults of foreign agents. On the other hand, dysregulated activation of ILCs could contribute to tissue inflammatory diseases. In spite of recent progress towards understanding roles of ILCs in the health and disease, mechanisms regulating specific establishment, activation, and function of ILCs in barrier tissues are still poorly understood. We herein review the up-to-date understanding of tissue-specific relevance of ILCs. Particularly we will focus on resident ILCs of the skin, the outmost barrier tissue critical in protection against various foreign hazardous agents and maintenance of thermal and water balance. In addition, we will discuss remaining outstanding questions yet to be addressed.

  14. Bronchus Associated Lymphoid Tissue Lymphoma Presenting with Immunodeficiency and Multiple Pulmonary Nodules

    PubMed Central

    Ozbalak, Murat; Ersen, Ezel; Akı, Hilal; Cem Ar, Muhlis; Umut, Sema

    2017-01-01

    Bronchus Associated Lymphoid Tissue Lymphoma (BALTOMA) is a rare subgroup of pulmonary non-Hodgkin's lymphomas (NHLs) comprising less than 1% of all cases. It constitutes 3.6% of all extranodal lymphomas and only 0.5–1% of primary pulmonary malignancies. They are usually low grade B-cell lymphomas and are considered to originate from the mucosa associated lymphoid tissue (MALT) of the bronchi. Here, we represent a rare case of BALTOMA presenting with immunodeficiency and multiple pulmonary nodules. PMID:28386504

  15. Adaptation of solitary intestinal lymphoid tissue in response to microbiota and chemokine receptor CCR7 signaling.

    PubMed

    Pabst, Oliver; Herbrand, Heike; Friedrichsen, Michaela; Velaga, Sarvari; Dorsch, Martina; Berhardt, Günter; Worbs, Tim; Macpherson, Andrew J; Förster, Reinhold

    2006-11-15

    Besides Peyer's patches, solitary intestinal lymphoid tissue (SILT) provides a structural platform to efficiently initiate immune responses in the murine small intestine. SILT consists of dynamic lymphoid aggregates that are heterogeneous in size and composition, ranging from small clusters of mostly lineage-negative cells known as cryptopatches to larger isolated lymphoid follicles rich in B cells. In this study, we report that in chemokine receptor CCR7-deficient mice SILT is enlarged, although unchanged in frequency and cellular composition compared with wild-type mice. This phenotype is conferred by bone marrow-derived cells and is independent of the presence of intestinal bacteria. Remarkably, particularly small-sized SILT predominates in germfree wild-type mice. Colonization of wild-type mice with commensal bacteria provokes an adjustment of the spectrum of SILT to that observed under specific pathogen-free conditions by the conversion of pre-existing lymphoid structures into larger-sized SILT. In conclusion, our findings establish that intestinal microbes influence the manifestation of gut-associated lymphoid tissues and identify CCR7 signaling as an endogeneous factor that controls this process.

  16. Post-conversion sialylation of prions in lymphoid tissues

    PubMed Central

    Srivastava, Saurabh; Makarava, Natallia; Katorcha, Elizaveta; Savtchenko, Regina; Brossmer, Reinhard; Baskakov, Ilia V.

    2015-01-01

    Sialylated glycans on the surface of mammalian cells act as part of a “self-associated molecular pattern,” helping the immune system to recognize “self” from “altered self” or “nonself.” To escape the host immune system, some bacterial pathogens have evolved biosynthetic pathways for host-like sialic acids, whereas others recruited host sialic acids for decorating their surfaces. Prions lack nucleic acids and are not conventional pathogens. Nevertheless, prions might use a similar strategy for invading and colonizing the lymphoreticular system. Here we show that the sialylation status of the infectious, disease-associated state of the prion protein (PrPSc) changes with colonization of secondary lymphoid organs (SLOs). As a result, spleen-derived PrPSc is more sialylated than brain-derived PrPSc. Enhanced sialylation of PrPSc is recapitulated in vitro by incubating brain-derived PrPSc with primary splenocytes or cultured macrophage RAW 264.7 cells. General inhibitors of sialyltranserases (STs), the enzymes that transfer sialic acid residues onto terminal positions of glycans, suppressed extrasialylation of PrPSc. A fluorescently labeled precursor of sialic acid revealed ST activity associated with RAW macrophages. This study illustrates that, upon colonization of SLOs, the sialylation status of prions changes by host STs. We propose that this mechanism is responsible for camouflaging prions in SLOs and has broad implications. PMID:26627256

  17. Suppression of HIV replication by lymphoid tissue CD8+ cells correlates with the clinical state of HIV-infected individuals

    PubMed Central

    Blackbourn, David J.; Mackewicz, Carl E.; Barker, Edward; Hunt, Thomas K.; Herndier, Brian; Haase, Ashley T.; Levy, Jay A.

    1996-01-01

    Lymphoid tissues from asymptomatic HIV-infected individuals, as compared with symptomatic HIV-infected subjects, show limited histopathological changes and lower levels of HIV expression. In this report we correlate the control of HIV replication in lymph nodes to the non-cytolytic anti-HIV activity of lymphoid tissue CD8+ cells. Five subjects at different stages of HIV-related disease were studied and the ability of their CD8+ cells, isolated from both lymphoid tissue and peripheral blood, to inhibit HIV replication was compared. CD8+ cells from lymphoid tissue and peripheral blood of two HIV-infected long-term survivors suppressed HIV replication at a low CD8+:CD4+ cell ratio of 0.1. The CD8+ cells from the lymphoid tissue of a third asymptomatic subject suppressed HIV replication at a CD8+:CD4+ cell ratio of 0.25; the subject’s peripheral blood CD8+ cells showed this antiviral response at a lower ratio of 0.05. The lymphoid tissue CD8+ cells from two AIDS patients were not able to suppress HIV replication, and the peripheral blood CD8+ cells of only one of them suppressed HIV replication. The plasma viremia, cellular HIV load as well as the extent of pathology and virus expression in the lymphoid tissue of the two long-term survivors, were reduced compared with these parameters in the three other subjects. The data suggest that the extent of anti-HIV activity by CD8+ cells from lymphoid tissue relative to peripheral blood correlates best with the clinical state measured by lymphoid tissue pathology and HIV burden in lymphoid tissues and blood. The results add further emphasis to the importance of this cellular immune response in controlling HIV pathogenesis. PMID:8917555

  18. Suppression of HIV Replication by Lymphoid Tissue CD8+ Cells Correlates with the Clinical State of HIV-Infected Individuals

    NASA Astrophysics Data System (ADS)

    Blackbourn, David J.; Mackewicz, Carl E.; Barker, Edward; Hunt, Thomas K.; Herndier, Brian; Haase, Ashley T.; Levy, Jay A.

    1996-11-01

    Lymphoid tissues from asymptomatic HIV-infected individuals, as compared with symptomatic HIV-infected subjects, show limited histopathological changes and lower levels of HIV expression. In this report we correlate the control of HIV replication in lymph nodes to the non-cytolytic anti-HIV activity of lymphoid tissue CD8+ cells. Five subjects at different stages of HIV-related disease were studied and the ability of their CD8+ cells, isolated from both lymphoid tissue and peripheral blood, to inhibit HIV replication was compared. CD8+ cells from lymphoid tissue and peripheral blood of two HIV-infected long-term survivors suppressed HIV replication at a low CD8+:CD4+ cell ratio of 0.1. The CD8+ cells from the lymphoid tissue of a third asymptomatic subject suppressed HIV replication at a CD8+:CD4+ cell ratio of 0.25; the subject's peripheral blood CD8+ cells showed this antiviral response at a lower ratio of 0.05. The lymphoid tissue CD8+ cells from two AIDS patients were not able to suppress HIV replication, and the peripheral blood CD8+ cells of only one of them suppressed HIV replication. The plasma viremia, cellular HIV load as well as the extent of pathology and virus expression in the lymphoid tissue of the two long-term survivors, were reduced compared with these parameters in the three other subjects. The data suggest that the extent of anti-HIV activity by CD8+ cells from lymphoid tissue relative to peripheral blood correlates best with the clinical state measured by lymphoid tissue pathology and HIV burden in lymphoid tissues and blood. The results and further emphasis to the importance of this cellular immune response in controlling HIV pathogenesis.

  19. [Response of immune system and lymphoid tissue of respiratory and gastrointestinal organs to space flight factors].

    PubMed

    Sapin, M R; Erofeeva, L M; Grigorenko, D E

    1999-01-01

    The studies demonstrated that gamma-radiation drastically enhanced destructive processes and suppressed the mitotic activity of lymphocytes in the thymus and spleen. This resulted in the altered morphological picture of immune organs: the inversion of layers occurred in the thymus, the splenic white pulp increased by three times, lymphoid nodules with germinating centers disappeared, the marginal area became thinner. Following gamma-radiation, restorative processes in the thymus and spleen were noticeable just on day 3 and 7, respectively. However, the cell composition of murine immune organs failed to achieve control values by day 60 after exposure. Examining the responses of respiratory and digestive lymphoid tissue to acetaldehyde and drinking water organisms indicated that as the concentration of an acting agent and the time of exposure increased, there was lymphocytopoietic inhibition in the lymphoid formations whereas its small doses activated a local immune response.

  20. Bystander CD4+ T lymphocytes survive in HIV-infected human lymphoid tissue

    NASA Technical Reports Server (NTRS)

    Grivel, Jean-Charles; Biancotto, Angelique; Ito, Yoshinori; Lima, Rosangela G.; Margolis, Leonid B.

    2003-01-01

    HIV infection is associated with depletion of CD4(+) T cells. The mechanisms of this phenomenon remain to be understood. In particular, it remains controversial whether and to what extent uninfected ("bystander") CD4(+) T cells die in HIV-infected individuals. We address this question using a system of human lymphoid tissue ex vivo. Tissue blocks were inoculated with HIV-1. After productive infection was established, they were treated with the reverse transcriptase inhibitor nevirapine to protect from infection those CD4(+) T cells that had not yet been infected. These CD4(+) T cells residing in HIV-infected tissue are by definition bystanders. Our results demonstrate that after nevirapine application the number of bystander CD4(+) T cells is conserved. Thus, in the context of HIV-infected human lymphoid tissue, productive HIV infection kills infected cells but is not sufficient to cause the death of a significant number of uninfected CD4(+) T cells.

  1. Bystander CD4+ T lymphocytes survive in HIV-infected human lymphoid tissue

    NASA Technical Reports Server (NTRS)

    Grivel, Jean-Charles; Biancotto, Angelique; Ito, Yoshinori; Lima, Rosangela G.; Margolis, Leonid B.

    2003-01-01

    HIV infection is associated with depletion of CD4(+) T cells. The mechanisms of this phenomenon remain to be understood. In particular, it remains controversial whether and to what extent uninfected ("bystander") CD4(+) T cells die in HIV-infected individuals. We address this question using a system of human lymphoid tissue ex vivo. Tissue blocks were inoculated with HIV-1. After productive infection was established, they were treated with the reverse transcriptase inhibitor nevirapine to protect from infection those CD4(+) T cells that had not yet been infected. These CD4(+) T cells residing in HIV-infected tissue are by definition bystanders. Our results demonstrate that after nevirapine application the number of bystander CD4(+) T cells is conserved. Thus, in the context of HIV-infected human lymphoid tissue, productive HIV infection kills infected cells but is not sufficient to cause the death of a significant number of uninfected CD4(+) T cells.

  2. Cytokine receptor expression in human lymphoid tissue: analysis by fluorescence microscopy.

    PubMed

    Zola, H; Ridings, J; Weedon, H; Fusco, M; Byard, R W; Macardle, P J

    1995-08-01

    A highly-sensitive flourescence method, capable of detecting cytokine receptors present at low concentrations (around 100 molecules per cell) by flow cytometry, was adapted for use on tissue sections. This method was used to examine the expression of several cytokine receptors in lymphoid tissues. IL-2 receptors were distributed broadly, with higher concentrations in T cell areas. IL-1 receptor Type 1 was detected in T cell areas and in the follicular mantle, and was strongly expressed on vascular endothelium. IL-6 receptor was found at very low concentration, both within and outside germinal centres. The gp 130 molecule, which is involved in the functional receptor complex for IL-6 and several other cytokines, was present at higher concentrations, particularly in the germinal centre. Analysis of receptor expression in secondary lymphoid tissue provides evidence bearing on the physiological roles of cytokines, as these tissues contain cells at various stages of physiological activation located in well-defined functional zones.

  3. Constitutive expression of tenascin in T-dependent zones of human lymphoid tissues.

    PubMed Central

    Chilosi, M.; Lestani, M.; Benedetti, A.; Montagna, L.; Pedron, S.; Scarpa, A.; Menestrina, F.; Hirohashi, S.; Pizzolo, G.; Semenzato, G.

    1993-01-01

    Tenascin is a major extracellular matrix glycoprotein that can interfere with the action of fibronectin by inhibiting cell adhesion and spreading. Although tenascin is able to exert important immunomodulatory activities on T and B cells and macrophages, little is known about its distribution in different lymphohemopoietic tissues. In this study we have analyzed tenascin immunoreactivity on cryostat and paraffin sections of normal and pathological lymphoid tissues using two different monoclonal antibodies. We demonstrated strong tenascin expression in all peripheral lymphoid tissues, whereas it was barely detectable in the thymus and in bone marrow. In reactive lymph nodes, tenascin was mainly found in T-dependent zones, forming a variably close-woven reticular network corresponding to fibroblastic reticulum cells and blood vessels basal laminae, showing a partial co-localization with fibronectin. In B-dependent zones, tenascin was restricted to blood vessels. Using double-marker analysis, we performed a thorough study comparing tenascin expression in different compartments of lymphoid microenvironments. Tenascin network appeared much thicker in chronically stimulated tissues, where CD4+ lymphocytes with "memory" phenotype (CD45RO+/CD45RA-) were predominant, and at sites of ongoing inflammation. In particular, a striking increase of tenascin was observed in sarcoid lymph node, as well as in myasthenic hyperplastic thymuses. In addition, tenascin can be abnormally synthesized in tissue involved by various types of lymphomas, including Hodgkin's disease and hairy cell leukemia. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:7694469

  4. African Lungfish Reveal the Evolutionary Origins of Organized Mucosal Lymphoid Tissue in Vertebrates

    PubMed Central

    Tacchi, Luca; Larragoite, Erin T.; Muñoz, Pilar; Amemiya, Chris T.

    2016-01-01

    SUMMARY One of the most remarkable innovations of the vertebrate adaptive immune system is the progressive organization of the lymphoid tissues that leads to increased efficiency of immune surveillance and cell interactions. The mucosal immune system of endotherms has evolved organized secondary mucosal lymphoid tissues (O-MALT) such as Peyer’s patches, tonsils, and adenoids. Primitive semi-organized lymphoid nodules or aggregates (LAs) were found in the mucosa of anuran amphibians [1], suggesting that O-MALT evolved from amphibian LAs_250 million years ago [1–4]. This study shows for the first time the presence of O-MALT in the mucosa of the African lungfish, an extant representative of the closest ancestral lineage to all tetrapods. Lungfish LAs are lymphocyte-rich structures associated with a modified covering epithelium and express all IGH genes except for IGHW2L. In response to infection, nasal LAs doubled their size and increased the expression of CD3 and IGH transcripts. Additionally, de novo organogenesis of inducible LAs resembling mammalian tertiary lymphoid structures was observed. Using deep-sequencing transcriptomes, we identified several members of the tumor necrosis factor (TNF) superfamily, and subsequent phylogenetic analyses revealed its extraordinary diversification within sarcopterygian fish. Attempts to find AICDA in lungfish transcriptomes or by RT-PCR failed, indicating the possible absence of somatic hypermutation in lungfish LAs. These findings collectively suggest that the origin of O-MALT predates the emergence of tetrapods and that TNF family members play a conserved role in the organization of vertebrate mucosal lymphoid organs. PMID:26344090

  5. African Lungfish Reveal the Evolutionary Origins of Organized Mucosal Lymphoid Tissue in Vertebrates.

    PubMed

    Tacchi, Luca; Larragoite, Erin T; Muñoz, Pilar; Amemiya, Chris T; Salinas, Irene

    2015-09-21

    One of the most remarkable innovations of the vertebrate adaptive immune system is the progressive organization of the lymphoid tissues that leads to increased efficiency of immune surveillance and cell interactions. The mucosal immune system of endotherms has evolved organized secondary mucosal lymphoid tissues (O-MALT) such as Peyer's patches, tonsils, and adenoids. Primitive semi-organized lymphoid nodules or aggregates (LAs) were found in the mucosa of anuran amphibians, suggesting that O-MALT evolved from amphibian LAs ∼250 million years ago. This study shows for the first time the presence of O-MALT in the mucosa of the African lungfish, an extant representative of the closest ancestral lineage to all tetrapods. Lungfish LAs are lymphocyte-rich structures associated with a modified covering epithelium and express all IGH genes except for IGHW2L. In response to infection, nasal LAs doubled their size and increased the expression of CD3 and IGH transcripts. Additionally, de novo organogenesis of inducible LAs resembling mammalian tertiary lymphoid structures was observed. Using deep-sequencing transcriptomes, we identified several members of the tumor necrosis factor (TNF) superfamily, and subsequent phylogenetic analyses revealed its extraordinary diversification within sarcopterygian fish. Attempts to find AICDA in lungfish transcriptomes or by RT-PCR failed, indicating the possible absence of somatic hypermutation in lungfish LAs. These findings collectively suggest that the origin of O-MALT predates the emergence of tetrapods and that TNF family members play a conserved role in the organization of vertebrate mucosal lymphoid organs. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Establishment of an in vitro system representing the chicken gut-associated lymphoid tissue.

    PubMed

    Alitheen, Noorjahan Banu; McClure, Susan Jane; Yeap, Swee Keong; Kristeen-Teo, Ye Wen; Tan, Sheau Wei; McCullagh, Peter

    2012-01-01

    The bursa of Fabricius is critical for B cell development and differentiation in chick embryos. This study describes the production in vitro, from dissociated cell suspensions, of cellular agglomerates with functional similarities to the chicken bursa. Co-cultivation of epithelial and lymphoid cells obtained from embryos at the appropriate developmental stage regularly led to agglomerate formation within 48 hours. These agglomerates resembled bursal tissue in having lymphoid clusters overlaid by well organized epithelium. Whereas lymphocytes within agglomerates were predominantly Bu-1a(+), a majority of those emigrating onto the supporting membrane were Bu-1a(-) and IgM(+). Both agglomerates and emigrant cells expressed activation-induced deaminase with levels increasing after 24 hours. Emigrating cells were actively proliferating at a rate in excess of both the starting cell population and the population of cells remaining in agglomerates. The potential usefulness of this system for investigating the response of bursal tissue to avian Newcastle disease virus (strain AF2240) was examined.

  7. Duodenal Mucosa-Associated Lymphoid Tissue Lymphomas: Two Cases and the Evaluation of Endoscopic Ultrasonography

    PubMed Central

    Kim, Su Jin; Choi, Choel Woong; Ha, Jong Kun; Hong, Young Mi; Park, Jin Hyun; Park, Soo Bum; Kang, Dae Hwan

    2013-01-01

    Mucosa-associated lymphoid tissue lymphoma mainly arises in the stomach, with fewer than 30% arising in the small intestine. We describe here two cases of primary duodenal mucosa-associated lymphoid tissue lymphoma which were evaluated by endoscopic ultrasonography. A 52-year-old man underwent endoscopy due to abdominal pain, which demonstrated a depressed lesion on duodenal bulb. Endoscopic ultrasonographic finding was hypoechoic lesion invading the submucosa. The other case was a previously healthy 51-year-old man. Endoscopy showed a whitish granular lesion on duodenum third portion. Endoscopic ultrasonography image was similar to the first case, whereas abdominal computed tomography revealed enlargement of multiple lymph nodes. The first case was treated with eradication of Helicobacter pylori, after which the mucosal change and endoscopic ultrasound finding were normalized in 7 months. The second case was treated with cyclophosphamide, vincristine, prednisolone, and rituximab every 3 weeks. After 6 courses of chemotherapy, the patient achieved complete remission. PMID:24143321

  8. Neutrophils and monocytes transport tumor cell antigens from the peritoneal cavity to secondary lymphoid tissues

    SciTech Connect

    Terasawa, Masao; Nagata, Kisaburo; Kobayashi, Yoshiro

    2008-12-12

    Antigen-transporting cells take up pathogens, and then migrate from sites of inflammation to secondary lymphoid tissues to induce an immune response. Among antigen-transporting cells, dendritic cells (DCs) are believed to be the most potent and professional antigen-presenting cells that can stimulate naive T cells. However, the cells that transport antigens, tumor cell antigens in particular, have not been clearly identified. In this study we have analyzed what types of cells transport tumor cell antigens to secondary lymphoid tissues. We show that neutrophils, monocytes and macrophages but not DCs engulf X-irradiated P388 leukemic cells after their injection into the peritoneal cavity, and that neutrophils and monocytes but not macrophages migrate to the parathymic lymph nodes (pLN), the blood, and then the spleen. The monocytes in the pLN comprise Gr-1{sup -} and Gr-1{sup +} ones, and some of these cells express CD11c. Overall, this study demonstrates that neutrophils and monocytes transport tumor cell antigens from the peritoneal cavity to secondary lymphoid tissues.

  9. Ectopic Tertiary Lymphoid Tissue in Inflammatory Bowel Disease: Protective or Provocateur?

    PubMed Central

    McNamee, Eóin N.; Rivera-Nieves, Jesús

    2016-01-01

    Organized lymphoid tissues like the thymus first appeared in jawed vertebrates around 500 million years ago and have evolved to equip the host with a network of specialized sites, strategically located to orchestrate strict immune-surveillance and efficient immune responses autonomously. The gut-associated lymphoid tissues maintain a mostly tolerant environment to dampen our responses to daily dietary and microbial products in the intestine. However, when this homeostasis is perturbed by chronic inflammation, the intestine is able to develop florid organized tertiary lymphoid tissues (TLT), which heralds the onset of regional immune dysregulation. While TLT are a pathologic hallmark of Crohn’s disease (CD), their role in the overall process remains largely enigmatic. A critical question remains; are intestinal TLT generated by the immune infiltrated intestine to modulate immune responses and rebuild tolerance to the microbiota or are they playing a more sinister role by generating dysregulated responses that perpetuate disease? Herein, we discuss the main theories of intestinal TLT neogenesis and focus on the most recent findings that open new perspectives to their role in inflammatory bowel disease. PMID:27579025

  10. IMP-3 is differentially expressed in normal and neoplastic lymphoid tissue.

    PubMed

    King, Rebecca L; Pasha, Theresa; Roullet, Michele R; Zhang, Paul J; Bagg, Adam

    2009-12-01

    IMP-3 is a member of the insulin-like growth factor II mRNA binding protein (IMP) family of proteins that play a role in RNA trafficking and stabilization and cell growth and migration during embryogenesis but which are down-regulated in adult tissue. However, IMP-3 has recently been shown to be overexpressed in several epithelial malignancies, with increased expression correlating with aggressive behavior. To our knowledge, there is no published literature evaluating IMP-3 in lymphoid tissue. Accordingly, we immunohistochemically evaluated IMP-3 expression in normal lymphoid tissue and 141 lymphoid neoplasms. Physiologically, IMP-3 expression was restricted to germinal center B cells. Among lymphoid neoplasms, Hodgkin lymphoma demonstrated the highest percentage of positive cases (26/26, 100%) often with bright staining. Burkitt lymphoma was positive in 10 (83%) of 12 cases with moderate to bright staining. Although follicular lymphoma was also positive in a high percentage of cases (12/15, 80%), the intensity was exclusively weak to moderate. Although 22 (85%) of 26 of diffuse large B-cell lymphomas were positive for IMP-3, there was wide variability in staining intensity, which did not correlate with classification into activated B cell versus germinal center B origin. By contrast, lower proportions (8%-20%) of other non-germinal center B lymphoma subtypes were IMP-3-positive. In conclusion, although IMP-3 expression is seemingly restricted to physiologic germinal center B cells, its expression in lymphomas of germinal center B origin is less robust. However, there does appear to be some association with the latter group of lymphomas, which may prove to have diagnostic or therapeutic relevance as the biologic role of IMP-3 is further elucidated.

  11. Spatially resolved microfluidic stimulation of lymphoid tissue ex vivo.

    PubMed

    Ross, Ashley E; Belanger, Maura C; Woodroof, Jacob F; Pompano, Rebecca R

    2016-11-30

    The lymph node is a structurally complex organ of the immune system, whose dynamic cellular arrangements are thought to control much of human health. Currently, no methods exist to precisely stimulate substructures within the lymph node or analyze local stimulus-response behaviors, making it difficult to rationally design therapies for inflammatory disease. Here we describe a novel integration of live lymph node slices with a microfluidic system for local stimulation. Slices maintained the cellular organization of the lymph node while making its core experimentally accessible. The 3-layer polydimethylsiloxane device consisted of a perfusion chamber stacked atop stimulation ports fed by underlying microfluidic channels. Fluorescent dextrans similar in size to common proteins, 40 and 70 kDa, were delivered to live lymph node slices with 284 ± 9 μm and 202 ± 15 μm spatial resolution, respectively, after 5 s, which is sufficient to target functional zones of the lymph node. The spread and quantity of stimulation were controlled by varying the flow rates of delivery; these were predictable using a computational model of isotropic diffusion and convection through the tissue. Delivery to two separate regions simultaneously was demonstrated, to mimic complex intercellular signaling. Delivery of a model therapeutic, glucose-conjugated albumin, to specific regions of the lymph node indicated that retention of the drug was greater in the B-cell zone than in the T-cell zone. Together, this work provides a novel platform, the lymph node slice-on-a-chip, to target and study local events in the lymph node and to inform the development of new immunotherapeutics.

  12. Morphological and functional development of the interbranchial lymphoid tissue (ILT) in Atlantic salmon (Salmo salar L).

    PubMed

    Dalum, Alf Seljenes; Griffiths, David James; Valen, Elin Christine; Amthor, Karoline Skaar; Austbø, Lars; Koppang, Erling Olaf; Press, Charles McLean; Kvellestad, Agnar

    2016-11-01

    The interbranchial lymphoid tissue (ILT) of Atlantic salmon originates from an embryological location that in higher vertebrates gives rise to both primary and secondary lymphoid tissues. Still much is unknown about the morphological and functional development of the ILT. In the present work a standardized method of organ volume determination was established to study its development in relation to its containing gill and the thymus. Based on morphological findings and gene transcription data, the ILT shows no signs of primary lymphoid function. In contrast to the thymus, an ILT-complex first became discernible after the yolk-sac period. After its appearance, the ILT-complex constitutes 3-7% of the total volume of the gill (excluding the gill arch) with the newly described distal ILT constituting a major part, and in adult fish it is approximately 13 times larger than the thymus. Confined regions of T-cell proliferation are present within the ILT. Communication with systemic circulation through the distal ILT is also highly plausible thus offering both internal and external recruitment of immune cells in the growing ILT.

  13. Histopathological and immunohistochemical findings in lymphoid tissues of the endangered Iberian lynx (Lynx pardinus).

    PubMed

    Peña, Laura; Garcia, Pilar; Jiménez, Maria Angeles; Benito, Alberto; Pérez Alenza, Maria Dolores; Sánchez, Belén

    2006-01-01

    The Iberian lynx (Lynx pardinus) is the most threatened wild feline in the world. Little is known about the diseases and pathology that affect this animal. The aim of this study was to evaluate the histopathological status of the peripheral lymphoid tissues and thymus of Iberian lynxes necropsied between 1998 and 2003. Seventeen animals including females (n=8) and males (n=9), age range of 10 months to 16 years, with different causes of death were histopathologically and immunohistochemically (anti-CD3, CD79, MAC387, CD68) studied. Feline immunosuppressive virus laboratorial tests were negative. Five individuals presented neoplasia and/or tuberculosis. All animals presented some degree of both B and T cells depletion in peripheral lymphoid tissues and follicular hyalinosis in the center of depleted follicles. A viral origin of the lymphoid depletion is postulated although other causes (inbreeding, stress, toxic) are not ruled out. The loss of the effectiveness of the immune system increases the vulnerability of the critically endangered Iberian lynx to pathogens.

  14. Detection of Mycobacterium avium subspecies in the gut associated lymphoid tissue of slaughtered rabbits.

    PubMed

    Arrazuria, Rakel; Sevilla, Iker A; Molina, Elena; Pérez, Valentín; Garrido, Joseba M; Juste, Ramón A; Elguezabal, Natalia

    2015-06-11

    Rabbits are susceptible to infection by different species of the genus Mycobacterium. Particularly, development of specific lesions and isolation of Mycobacterium avium subsp. avium and Mycobacterium avium subsp. paratuberculosis, both subspecies of the M. avium complex, has been reported in wildlife conditions. Although, rabbit meat production worldwide is 200 million tons per year, microbiological data on this source of meat is lacking and more specifically reports of mycobacterial presence in industrially reared rabbit for human consumption have not been published. To this end, we sought mycobacteria by microbiological and histopathological methods paying special attention to Mycobacterium avium subsp. paratuberculosis in rabbits from commercial rabbitries from the North East of Spain. M. avium subsp. paratuberculosis was not detected either by culture or PCR. However, Mycobacterium avium subsp. avium was detected in 15.15% (10/66) and Mycobacterium avium subsp. hominissuis was detected in 1.51% (1/66) of gut associated lymphoid tissue of sampled animals by PCR, whereas caecal contents were negative. 9% (6/66) of the animals presented gross lesions suggestive of lymphoid activation, 6% (4/66) presented granulomatous lesions and 3% (2/66) contained acid fast bacilli. Mycobacterial isolation from samples was not achieved, although colonies of Thermoactinomycetes sp. were identified by 16s rRNA sequencing in 6% (4/66) of sampled animals. Apparently healthy farmed rabbits that go to slaughter may carry M. avium subspecies in gut associated lymphoid tissue.

  15. CD4+ lymphoid tissue inducer cells promote innate immunity in the gut

    PubMed Central

    Sonnenberg, Gregory F.; Monticelli, Laurel A.; Elloso, M. Merle; Fouser, Lynette A.; Artis, David

    2010-01-01

    SUMMARY Fetal CD4+ lymphoid tissue inducer (LTi) cells play a critical role in the development of lymphoid-tissues. Recent studies identified that LTi cells persist in adults and are related to a heterogeneous population of innate lymphoid cells that have been implicated in inflammatory responses. However, whether LTi cells contribute to protective immunity remains poorly defined. We demonstrate that following infection with Citrobacter rodentium, CD4+ LTi cells were a dominant source of interleukin-22 (IL-22) early during infection. Infection-induced CD4+ LTi cell responses were IL-23-dependent, and ablation of IL-23 impaired innate immunity. Further, depletion of CD4+ LTi cells abrogated infection-induced expression of IL-22 and anti-microbial peptides, resulting in exacerbated host mortality. LTi cells were also found to be essential for host protective immunity in lymphocyte-replete hosts. Collectively these data demonstrate that adult CD4+ LTi cells are a critical source of IL-22 and identify a previously unrecognized function for CD4+ LTi cells in promoting innate immunity in the intestine. PMID:21194981

  16. A histological and immunohistochemical analysis of lymphoid tissues of the Tasmanian devil.

    PubMed

    Kreiss, Alexandre; Obendorf, David L; Hemsley, Susan; Canfield, Paul J; Woods, Gregory M

    2009-05-01

    Tasmanian devil lymphoid tissues (thymus, spleen, and lymph node) from seven animals, including pouch young, juvenile, and adult devils, were investigated using histological and immunohistochemical techniques. Antibodies against the conserved intracytoplasmic portion of CD3 and CD79b (T- and B-cell markers, respectively) and MHC II were used to label immune cells. The thymus from the juvenile devils and the pouch young had CD3+ cells that were primarily located in the medulla of the organ. The spleen consisted of red and white pulp areas with characteristic lymphoid follicles with CD79b+ and MHC II+ cells and nonfollicular T-cell-dominated periarteriolar lymphoid sheaths. Peripheral lymph nodes presented three distinct regions, outer cortex and medulla (both with primarily CD79b+ and MHC II+ cells) and paracortex (mainly CD3+ cells). Tissue architecture and distribution of the immune cells were similar to that seen in eutherian mammals and other marsupials, indicating that the Tasmanian devil has all the structural elements necessary for effective adaptive immunity.

  17. Inducible Bronchus-Associated Lymphoid Tissue: Taming Inflammation in the Lung

    PubMed Central

    Hwang, Ji Young; Randall, Troy D.; Silva-Sanchez, Aaron

    2016-01-01

    Following pulmonary inflammation, leukocytes that infiltrate the lung often assemble into structures known as inducible Bronchus-Associated Lymphoid Tissue (iBALT). Like conventional lymphoid organs, areas of iBALT have segregated B and T cell areas, specialized stromal cells, high endothelial venules, and lymphatic vessels. After inflammation is resolved, iBALT is maintained for months, independently of inflammation. Once iBALT is formed, it participates in immune responses to pulmonary antigens, including those that are unrelated to the iBALT-initiating antigen, and often alters the clinical course of disease. However, the mechanisms that govern immune responses in iBALT and determine how iBALT impacts local and systemic immunity are poorly understood. Here, we review our current understanding of iBALT formation and discuss how iBALT participates in pulmonary immunity. PMID:27446088

  18. Multispectral imaging reveals the tissue distribution of tetraspanins in human lymphoid organs.

    PubMed

    de Winde, Charlotte M; Zuidscherwoude, Malou; Vasaturo, Angela; van der Schaaf, Alie; Figdor, Carl G; van Spriel, Annemiek B

    2015-08-01

    Multispectral imaging is a novel microscopy technique that combines imaging with spectroscopy to obtain both quantitative expression data and tissue distribution of different cellular markers. Tetraspanins CD37 and CD53 are four-transmembrane proteins involved in cellular and humoral immune responses. However, comprehensive immunohistochemical analyses of CD37 and CD53 in human lymphoid organs have not been performed so far. We investigated CD37 and CD53 protein expression on primary human immune cell subsets in blood and in primary and secondary lymphoid organs. Both tetraspanins were prominently expressed on antigen-presenting cells, with highest expression of CD37 on B lymphocytes. Analysis of subcellular distribution showed presence of both tetraspanins on the plasma membrane and on endosomes. In addition, CD53 was also present on lysosomes. Quantitative analysis of expression and localization of CD37 and CD53 on lymphocytes within lymphoid tissues by multispectral imaging revealed high expression of both tetraspanins on CD20(+) cells in B cell follicles in human spleen and appendix. CD3(+) T cells within splenic T cell zones expressed lower levels of CD37 and CD53 compared to T cells in the red pulp of human spleen. B cells in human bone marrow highly expressed CD37, whereas the expression of CD53 was low. In conclusion, we demonstrate differential expression of CD37 and CD53 on primary human immune cells, their subcellular localization and their quantitative distribution in human lymphoid organs. This study provides a solid basis for better insight into the function of tetraspanins in the human immune response.

  19. Microbiota-induced tertiary lymphoid tissues aggravate inflammatory disease in the absence of RORγt and LTi cells

    PubMed Central

    Lochner, Matthias; Ohnmacht, Caspar; Presley, Laura; Bruhns, Pierre; Si-Tahar, Mustapha; Sawa, Shinichiro

    2011-01-01

    The programmed development of lymph nodes and Peyer’s patches during ontogeny requires lymphoid tissue inducer (LTi) cells that express the nuclear hormone receptor RORγt. After birth, LTi cells in the intestine cluster into cryptopatches, the precursors of isolated lymphoid follicles (ILFs), which are induced to form by symbiotic bacteria and maintain intestinal homeostasis. We show that in RORγt-deficient mice, which lack LTi cells, programmed lymphoid tissues, ILFs, and Th17 cells, bacterial containment requires the generation of large numbers of tertiary lymphoid tissues (tLTs) through the activity of B cells. However, upon epithelial damage, these mice develop severe intestinal inflammation characterized by extensive recruitment of neutrophils and IgG+ B cells, high expression of activation-induced deaminase in tLTs, and wasting disease. The pathology was prevented by antibiotic treatment or inhibition of lymphoid tissue formation and was significantly decreased by treatment with intravenous immunoglobulin G (IVIG). Our data show that intestinal immunodeficiency, such as an absence in RORγt-mediated proinflammatory immunity, can be compensated by increased lymphoid tissue genesis. However, this comes at a high cost for the host and can lead to a deregulated B cell response and aggravated inflammatory pathology. PMID:21173107

  20. Immunohistochemical study of lymphoid tissues in adjuvant arthritis (AA) by image analysis; relationship with synovial lesions

    PubMed Central

    Carol, M; Pelegrí, C; Castellote, C; Franch, A; Castell, M

    2000-01-01

    The aim of this study was to examine leucocyte populations in lymphoid organs during AA and to ascertain the relationship with lesions in synovial joints. Popliteal lymph nodes, spleen and knee synovial membranes were removed from both healthy and AA rats at intervals of 3–4 days over a 3-week period. Cryostat sections were stained with MoAbs directed against lymphocyte and macrophage subpopulations, and studied by image analysis. Throughout the arthritic period, high numbers of ED1+ and ED3+ macrophages were seen in both lymphoid compartments and intercellular adhesion molecule-1 (ICAM-1) expression also increased in some zones of lymph nodes and spleen. The percentages of CD4+ and CD8+ cells rose in the splenic zones studied but fell in the lymph node cortex. Very few natural killer (NK) cells were found in lymphoid tissues, but the number rose after AA induction. In synovia from AA rats, ED2+ macrophages proliferated but α/β T cell infiltration was only occasionally observed, accompanied by ED1+ cells and ICAM-1 expression. In conclusion, synovitis developing after AA induction seems to be caused directly by macrophages and indirectly by lymphocytes placed both in popliteal lymph nodes and spleen. PMID:10759784

  1. Electron Tomography of HIV-1 Infection in Gut-Associated Lymphoid Tissue

    PubMed Central

    Ladinsky, Mark S.; Kieffer, Collin; Olson, Gregory; Deruaz, Maud; Vrbanac, Vladimir; Tager, Andrew M.; Kwon, Douglas S.; Bjorkman, Pamela J.

    2014-01-01

    Critical aspects of HIV-1 infection occur in mucosal tissues, particularly in the gut, which contains large numbers of HIV-1 target cells that are depleted early in infection. We used electron tomography (ET) to image HIV-1 in gut-associated lymphoid tissue (GALT) of HIV-1–infected humanized mice, the first three-dimensional ultrastructural examination of HIV-1 infection in vivo. Human immune cells were successfully engrafted in the mice, and following infection with HIV-1, human T cells were reduced in GALT. Virions were found by ET at all stages of egress, including budding immature virions and free mature and immature viruses. Immuno-electron microscopy verified the virions were HIV-1 and showed CD4 sequestration in the endoplasmic reticulum of infected cells. Observation of HIV-1 in infected GALT tissue revealed that most HIV-1–infected cells, identified by immunolabeling and/or the presence of budding virions, were localized to intestinal crypts with pools of free virions concentrated in spaces between cells. Fewer infected cells were found in mucosal regions and the lamina propria. The preservation quality of reconstructed tissue volumes allowed details of budding virions, including structures interpreted as host-encoded scission machinery, to be resolved. Although HIV-1 virions released from infected cultured cells have been described as exclusively mature, we found pools of both immature and mature free virions within infected tissue. The pools could be classified as containing either mostly mature or mostly immature particles, and analyses of their proximities to the cell of origin supported a model of semi-synchronous waves of virion release. In addition to HIV-1 transmission by pools of free virus, we found evidence of transmission via virological synapses. Three-dimensional EM imaging of an active infection within tissue revealed important differences between cultured cell and tissue infection models and furthered the ultrastructural understanding

  2. Characterization of the diffuse mucosal associated lymphoid tissue of feline small intestine.

    PubMed

    Roccabianca, P; Woo, J C; Moore, P F

    2000-06-30

    Characterization of the feline intestinal mucosal associated lymphoid tissue (MALT) will facilitate investigation of intestinal disease in the cat and promote the cat as an animal model for a range of human diseases which involve the intestinal lymphoid tissue. This includes inflammatory bowel disease, viral and non-viral associated intestinal lymphomas and immunodeficiency associated syndromes. Morphologic and phenotypic characterization of the normal small intestinal diffuse MALT in 22 SPF cats was performed using flow cytometry and cytology on isolated intestinal leukocytes from the intra-epithelial and lamina proprial compartments, as well as immunohistology on tissues from the feline duodenum, jejunum and ileum. The intra-epithelial compartment (IEC) was dominated by lymphocytes (>85%) which frequently contained intracytoplasmic granules. The most striking findings in the IEC were the elevated percentages of CD8 alpha+ lymphocytes (40%), presumed to express CD8 alpha alpha chains, and CD4-/CD8- (double negative) lymphocytes (44%), and the consistent presence of a minor subpopulation of CD3+/CD11d+ IELs (6%). Small percentages of CD4+ lymphocytes (10%) were observed such that the IEL CD4:CD8 ratio (0.25) was low. The LPC also contained a majority of T cells and few plasma cells. However, this compartment had reduced percentages of CD8 alpha+ lymphocytes (28%) and increased percentages of CD4+ lymphocytes (27%) relative to the IEC. However, the LPL CD4:CD8 ratio (1.0) remained low compared with the ratio in peripheral blood. In feline MALT, MHC class II expression was lower than in other peripheral lymphoid compartments. The results of this study provide important reference values for future investigations involving feline intestinal lymphocytes and demonstrates that the leukocyte distribution and phenotypic characteristics of the feline diffuse MALT appear largely similar to the murine, rat and human counterparts.

  3. Regulation of murine lymphokine production in vivo. III. The lymphoid tissue microenvironment exerts regulatory influences over T helper cell function

    PubMed Central

    1990-01-01

    We investigated the capacity of murine T lymphocytes, isolated from various lymphoid organs of normal or antigen-primed donors, to produce IL-2 or IL-4 after activation with anti-CD3 or specific antigen. Our results established that T cells resident within lymphoid organs being drained by nonmucosal tissue sites (e.g., axillary, inguinal, brachial lymph nodes, or spleen) produced IL-2 as the predominant T cell growth factor (TCGF) after activation. Conversely, activated T cells from lymphoid organs being drained by mucosal tissues (Peyer's patches, and cervical, periaortic, and parathymic lymph nodes) produced IL-4 as the major species of TCGF. Analysis of the lymphoid tissues obtained from adoptive recipients of antigen-primed lymphocytes provided by syngeneic donors provided evidence that direct influences were being exerted on T cells during their residence within defined lymphoid compartments. These lymphoid tissue influences appeared to be responsible for altering the potential of resident T cells to produce distinct species of TCGF. Steroid hormones, known transcriptional enhancers and repressors of specific cellular genes, were implicated in the controlling mechanisms over TCGF production. Glucocorticoids (GCs) were found to exert a systemic effect on all recirculating T cells, evidenced by a marked dominance in IL-4 production by T cells obtained from all lymphoid organs of GC-treated mice, or after a direct exposure of normal lymphoid cells to GCs in vitro before cellular activation with T cell mitogens. Further, the androgen steroid DHEA appeared to be responsible for providing an epigenetic influence to T cells trafficking through peripheral lymphoid organs. This steroid influence resulted in an enhanced potential for IL-2 secretion after activation. Anatomic compartmentalization of the DHEA-facilitated influence appears to be mediated by differential levels of DHEA-sulfatase in lymphoid tissues. DHEA-sulfatase is an enzyme capable of converting DHEA

  4. Regulation of metabolic health and adipose tissue function by group 2 innate lymphoid cells.

    PubMed

    Cautivo, Kelly M; Molofsky, Ari B

    2016-06-01

    Adipose tissue (AT) is home to an abundance of immune cells. With chronic obesity, inflammatory immune cells accumulate and promote insulin resistance and the progression to type 2 diabetes mellitus. In contrast, recent studies have highlighted the regulation and function of immune cells in lean, healthy AT, including those associated with type 2 or "allergic" immunity. Although traditionally activated by infection with multicellular helminthes, AT type 2 immunity is active independently of infection, and promotes tissue homeostasis, AT "browning," and systemic insulin sensitivity, protecting against obesity-induced metabolic dysfunction and type 2 diabetes mellitus. In particular, group 2 innate lymphoid cells (ILC2s) are integral regulators of AT type 2 immunity, producing the cytokines interleukin-5 and IL-13, promoting eosinophils and alternatively activated macrophages, and cooperating with and promoting AT regulatory T (Treg) cells. In this review, we focus on the recent developments in our understanding of group 2 innate lymphoid cell cells and type 2 immunity in AT metabolism and homeostasis. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. The early interferon response of nasal-associated lymphoid tissue to Streptococcus pyogenes infection.

    PubMed

    Hyland, Kendra A; Brennan, Robert; Olmsted, Stephen B; Rojas, Eduardo; Murphy, Ellen; Wang, Beinan; Cleary, P Patrick

    2009-04-01

    Streptococcus pyogenes is a major causative agent of tonsillitis or pharyngitis in children. Streptococcus pyogenes can persist in tonsils, and one-third of children treated with antibiotics continue to shed streptococci and have recurrent infections. Mouse nasal-associated lymphoid tissue (NALT) is functionally analogous to human oropharyngeal lymphoid tissues, and serves as a model for characterization of the mucosal innate immune response to S. pyogenes. Wild-type S. pyogenes induces transcription of both type I and interferon-gamma (IFN-gamma)-responsive genes, proinflammatory genes and acute-phase response proteins 24 h after intranasal infection. Invasion of NALT and the induction of the interferon response were not dependent on expression of antiphagocytic M protein. Intranasal infection induces a substantial influx of neutrophils into NALT at 24 h, which declines by 48 h after infection. Infection of IFN-gamma(-/-) [IFN-gamma knock-out mouse (GKO)] C57BL/6 mice with wild-type S. pyogenes resulted in local dissemination of bacteria to draining lymph nodes (LN), but did not lead to systemic infection by 48 h after infection. Infected GKO mice had an increased influx of neutrophils into NALT compared with immunocompetent mice. Thus, IFN-gamma-induced responses are required to prevent local dissemination of streptococci to the draining LN.

  6. Aging affects B-cell antigen receptor repertoire diversity in primary and secondary lymphoid tissues.

    PubMed

    Tabibian-Keissar, Hilla; Hazanov, Lena; Schiby, Ginette; Rosenthal, Noemie; Rakovsky, Aviya; Michaeli, Miri; Shahaf, Gitit Lavy; Pickman, Yishai; Rosenblatt, Kinneret; Melamed, Doron; Dunn-Walters, Deborah; Mehr, Ramit; Barshack, Iris

    2016-02-01

    The elderly immune system is characterized by reduced responses to infections and vaccines, and an increase in the incidence of autoimmune diseases and cancer. Age-related deficits in the immune system may be caused by peripheral homeostatic pressures that limit bone marrow B-cell production or migration to the peripheral lymphoid tissues. Studies of peripheral blood B-cell receptor spectratypes have shown that those of the elderly are characterized by reduced diversity, which is correlated with poor health status. In the present study, we performed for the first time high-throughput sequencing of immunoglobulin genes from archived biopsy samples of primary and secondary lymphoid tissues in old (74 ± 7 years old, range 61-89) versus young (24 ± 5 years old, range 18-45) individuals, analyzed repertoire diversities and compared these to results in peripheral blood. We found reduced repertoire diversity in peripheral blood and lymph node repertoires from old people, while in the old spleen samples the diversity was larger than in the young. There were no differences in somatic hypermutation characteristics between age groups. These results support the hypothesis that age-related immune frailty stems from altered B-cell homeostasis leading to narrower memory B-cell repertoires, rather than changes in somatic hypermutation mechanisms. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. High-grade B-cell lymphoma arising in mucosa-associated lymphoid tissue of the duodenum.

    PubMed

    Leone, Nicola; Brunello, Franco; Baronio, Monica; Giordanino, Chiara; Morgando, Anna; Marchesa, Pierenrico; Delsedime, Luisa; Rizzetto, Mario

    2002-08-01

    Duodenal mucosa-associated lymphoid tissue lymphoma is a rare neoplasm. We report a case of a 70-year-old man with non-Hodgkin's lymphoma located in the descending duodenum that was not associated with Helicobacter pylori infection of the stomach. A surgical resection due to obstruction of the bowel lumen above the ligament of Treitz was performed. No invasion into the adjacent structure was confirmed at surgery. The pathological examination showed an infiltration of the duodenal mucosa and submucosa with B lymphocytes. Monoclonal proliferation of the lymphoid tissue was demonstrated by polymerase chain reaction. The histological appearance and the demonstration of monoclonality fulfilled the criteria for malignant high-grade B-cell lymphoma arising from mucosa-associated lymphoid tissue.

  8. Innate Lymphoid Cells: Balancing Immunity, Inflammation, and Tissue Repair in the Intestine

    PubMed Central

    Wojno, Elia D. Tait; Artis, David

    2012-01-01

    Innate lymphoid cells (ILCs) are a recently described group of innate immune cells that can regulate immunity, inflammation, and tissue repair in multiple anatomical compartments, particularly the barrier surfaces of the skin, airways, and intestine. Broad categories of ILCs have been defined based on transcription factor expression and the ability to produce distinct patterns of effector molecules. Recent studies have revealed that ILC populations can regulate commensal bacterial communities, contribute to resistance to helminth and bacterial pathogens, promote inflammation, and orchestrate tissue repair and wound healing. This review will examine the phenotype and function of murine and human ILCs and discuss the critical roles these innate immune cells play in health and disease. PMID:23084914

  9. Transcriptional programs of lymphoid tissue capillary and high endothelium reveal control mechanisms for lymphocyte homing

    PubMed Central

    Lee, Mike; Kiefel, Helena; LaJevic, Melissa D.; Macauley, Matthew S.; Kawashima, Hiroto; O'Hara, Edward; Pan, Junliang; Paulson, James C.; Butcher, Eugene C.

    2014-01-01

    Lymphocytes are recruited from blood by high-endothelial venules (HEVs). We performed transcriptomic analyses and identified molecular signatures that distinguish HEVs from capillary endothelium and that define tissue-specific HEV specialization. Capillaries displayed gene programs for vascular development. HEVs were enriched in genes for immune defense and lymphocyte migration. We identify capillary and HEV markers and candidate mechanisms for regulated lymphocyte recruitment including a lymph node HEV-selective transmembrane mucin; transcriptional control of functionally specialized carbohydrate ligands for lymphocyte L-selectin; HEV expression of molecules for transendothelial migration; and metabolic programs for lipid mediators of lymphocyte motility and chemotaxis. We also elucidate a carbohydrate recognition pathway that targets B cells to intestinal lymphoid tissues, defining CD22 as a lectin-homing receptor for mucosal HEVs. PMID:25173345

  10. Innate lymphoid cells promote lung tissue homeostasis following acute influenza virus infection

    PubMed Central

    Monticelli, Laurel A.; Sonnenberg, Gregory F.; Abt, Michael C.; Alenghat, Theresa; Ziegler, Carly G.K.; Doering, Travis A.; Angelosanto, Jill M.; Laidlaw, Brian J.; Yang, Cliff Y.; Sathaliyawala, Taheri; Kubota, Masaru; Turner, Damian; Diamond, Joshua M.; Goldrath, Ananda W.; Farber, Donna L.; Collman, Ronald G.; Wherry, E. John; Artis, David

    2012-01-01

    Innate lymphoid cells (ILCs), a recently identified heterogeneous cell population, are critical in orchestrating immunity and inflammation in the intestine but whether ILCs can influence immune responses or tissue homeostasis at other mucosal sites remains poorly characterized. Here we identify a population of lung-resident ILCs in mice and humans that expressed CD90, CD25, CD127 and T1-ST2. Strikingly, mouse ILCs accumulated in the lung following influenza virus infection and depletion of ILCs resulted in loss of airway epithelial integrity, decreased lung function and impaired airway remodeling. These defects could be restored by administration of the lung ILC product amphiregulin. Collectively, these results demonstrate a critical role for lung ILCs in restoring airway epithelial integrity and tissue homeostasis following influenza virus infection. PMID:21946417

  11. Type 3 innate lymphoid cells maintain intestinal epithelial stem cells after tissue damage.

    PubMed

    Aparicio-Domingo, Patricia; Romera-Hernandez, Monica; Karrich, Julien J; Cornelissen, Ferry; Papazian, Natalie; Lindenbergh-Kortleve, Dicky J; Butler, James A; Boon, Louis; Coles, Mark C; Samsom, Janneke N; Cupedo, Tom

    2015-10-19

    Disruption of the intestinal epithelial barrier allows bacterial translocation and predisposes to destructive inflammation. To ensure proper barrier composition, crypt-residing stem cells continuously proliferate and replenish all intestinal epithelial cells within days. As a consequence of this high mitotic activity, mucosal surfaces are frequently targeted by anticancer therapies, leading to dose-limiting side effects. The cellular mechanisms that control tissue protection and mucosal healing in response to intestinal damage remain poorly understood. Type 3 innate lymphoid cells (ILC3s) are regulators of homeostasis and tissue responses to infection at mucosal surfaces. We now demonstrate that ILC3s are required for epithelial activation and proliferation in response to small intestinal tissue damage induced by the chemotherapeutic agent methotrexate. Multiple subsets of ILC3s are activated after intestinal tissue damage, and in the absence of ILC3s, epithelial activation is lost, correlating with increased pathology and severe damage to the intestinal crypts. Using ILC3-deficient Lgr5 reporter mice, we show that maintenance of intestinal stem cells after damage is severely impaired in the absence of ILC3s or the ILC3 signature cytokine IL-22. These data unveil a novel function of ILC3s in limiting tissue damage by preserving tissue-specific stem cells.

  12. Successful treatment of mucosa-associated lymphoid tissue lymphoma of the rectum with radiation therapy: report of a case.

    PubMed

    Foo, Marcus; Chao, Michael W T; Gibbs, Peter; Guiney, Michael; Jacobs, Rodney

    2008-11-01

    We report a case of Stage IE mucosa-associated lymphoid tissue lymphoma arising in the rectum, which was successfully treated with radiotherapy. A 60-year-old man had several months of altered bowel habit with rectal bleeding and was found to have a large rectal tumor with no evidence of distant spread. Histologic studies showed this to be a mucosa-associated lymphoid tissue lymphoma. The patient received 45 Gy in 25 fractions with external beam radiotherapy during 5 weeks. The treatment was well tolerated and review at 41 months revealed no evidence of recurrence.

  13. Innate lymphoid cells: the role in respiratory infections and lung tissue damage.

    PubMed

    Głobińska, Anna; Kowalski, Marek L

    2017-10-01

    Innate lymphoid cells (ILCs) represent a diverse family of cells of the innate immune system, which play an important role in regulation of tissue homeostasis, immunity and inflammation. Emerging evidence has highlighted the importance of ILCs in both protective immunity to respiratory infections and their pathological roles in the lungs. Therefore, the aim of this review is to summarize the current knowledge, interpret and integrate it into broader perspective, enabling greater insight into the role of ILCs in respiratory diseases. Areas covered: In this review we highlighted the role of ILCs in the lungs, citing the most recent studies in this area. PubMed searches (2004- July 2017) were conducted using the term 'innate lymphoid cells respiratory viral infections' in combination with other relevant terms including various respiratory viruses. Expert commentary: Since studies of ILCs have opened new areas of investigation, understanding the role of ILCs in respiratory infections may help to clarify the mechanisms underlying viral-induced exacerbations of lung diseases, providing the basis for novel therapeutic strategies. Potential therapeutic targets have already been identified. So far, the most promising strategy is cytokine-targeting, although further clinical trials are needed to verify its effectiveness.

  14. Long-term immunologically competent human peripheral lymphoid tissue cultures in a 3D bioreactor

    PubMed Central

    Kuzin, Igor; Sun, Hongliang; Moshkani, Safiekhatoon; Feng, Changyong; Mantalaris, Athanasios; Wu, JH David; Bottaro, Andrea

    2011-01-01

    Peripheral lymphoid organs (PLOs), the primary sites of development of adaptive immune responses, display a complex structural organization reflecting separation of cellular subsets (e.g. T and B lymphocytes) and functional compartments which is critical for immune function. The generation of in vitro culture systems capable of recapitulating salient features of PLOs for experimental, biotechnological and clinical applications would be highly desirable, but has been hampered so far by the complexity of these systems. We have previously developed a three-dimensional bioreactor system for long-term, functional culture of human bone marrow cells on macroporous microspheres in a packed-bed bioreactor with frequent medium change. Here we adapt the same system for culture of human primary cells from PLOs (tonsil) in the absence of specific exogenous growth factors or activators. Cells in this system displayed higher viability over several weeks, and maintain population diversity and cell surface markers largely comparable to primary cells. Light microscopy showed cells organizing in large diverse clusters within the scaffold pores and presence of B cell-enriched areas. Strikingly, these cultures generated a significant number of antibody-producing B cells when challenged with a panel of diverse antigens, as expected from a lymphoid tissue. Thus the three-dimensional tonsil bioreactor culture system may serve as a useful model of PLOs by recapitulating their structural organization and function ex vivo. PMID:21309085

  15. Regulation of metabolic health and adipose tissue function by group 2 innate lymphoid cells

    PubMed Central

    Cautivo, Kelly M.; Molofsky, Ari B.

    2016-01-01

    Adipose tissue (AT) is home to an abundance of immune cells. With chronic obesity, inflammatory immune cells accumulate and promote insulin resistance and the progression to type 2 diabetes mellitus (T2DM). In contrast, recent studies have highlighted the regulation and function of immune cells in lean, healthy adipose tissue, including those associated with type 2 or “allergic” immunity. Although traditionally activated by infection with multicellular helminthes, AT type 2 immunity is active independently of infection, and promotes tissue homeostasis, adipose tissue “browning”, and systemic insulin sensitivity, protecting against obesity-induced metabolic dysfunction and T2DM. In particular, group 2 innate lymphoid cells (ILC2s) are integral regulators of AT type 2 immunity, producing the cytokines IL-5 and IL-13, promoting eosinophils and alternatively activated macrophages, and cooperating with and promoting AT regulatory T (Treg) cells. In this review, we focus on the recent developments in our understanding of ILC2 cells and type 2 immunity in adipose tissue metabolism and homeostasis. PMID:27120716

  16. Development, alteration and real time dynamics of conjunctiva-associated lymphoid tissue.

    PubMed

    Siebelmann, Sebastian; Gehlsen, Uta; Hüttmann, Gereon; Koop, Norbert; Bölke, Torsten; Gebert, Andreas; Stern, Michael E; Niederkorn, Jerry Y; Steven, Philipp

    2013-01-01

    Conjunctiva-associated lymphoid tissue (CALT) is thought to play a key role in initiating ocular surface related immune responses. This study was planned to get first profound insights into the function of CALT related to development, cellular dynamics and morphological alteration using a novel mouse model. Expression and morphology of CALT were investigated using BALB/c mice kept under different housing conditions, after topical antigen-stimulation and following lymphadenectomy and splenectomy. Particles and bacteria were applied topically to study antigen-transport. Intravital visualization was performed using two-photon microscopy. Postnatal development and ultrastructure of CALT in the mouse is similar to humans. Topical antigen-challenge significantly alters CALT expression. Bacterial translocation is demonstrated via lymphoepithelium whereas cellular velocities within follicles were approximately 8 µm/min. CALT in the mouse is an immunological interface of the ocular surface, featuring dynamic processes such as morphological plasticity, particle/bacteria transport and cellular migration.

  17. [Diagnosis and prognosis of reactive lymphoreticular hyperplasia (RLH) or mucosa-associated lymphoid tissue (MALT) lymphoma].

    PubMed

    Matsumoto, S; Kohda, K; Koike, K; Konuma, Y; Nakazawa, O; Ando, K; Teramoto, J; Takayama, T

    1998-08-01

    We studied the diagnostic significance of immunohistolochemical staining and immunoglobuline gene rearrangement of jumbo-biopsy specimen from 14 patients with stomach lesions which were difficult to distingwish between reactive lymphoreticular hyperplasia (RLH) and mucosa-associated lymphoid tissue lymphoma (MALT lymphoma). We also investigated Helicobacter pylori (HP) infection in the patients and followed their clinical courses from a mean observation period of 3 years and 4 months following initial diagnosis. As a result, 7 of the 14 cases were diagnosed as having MALT lymphoma. All of them were resected, and then the diagnosis was confirmed. Metastasis was found in 2 cases. The other 7 cases were diagnosed as RLH. A favorable prognosis during follow up without any treatment supported the belief that they were non-malignant lesions. HP infections were observed on 83% of the RLH cases and 57% of MALT lymphoma cases. In one of the case of RLH, the lesion disappeared after eradication of HP.

  18. [Gastric Mucosa-associated Lymphoid Tissue Lymphoma Based on Outcome of Domestic Treatment].

    PubMed

    Jung, Jin Tae

    2016-10-25

    Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is associated with Helicobacter pylori infection. H. pylori eradication can be performed as a primary therapy regardless of H. pylori status. In Korea, six articles were published about low-grade gastric MALT lymphoma with H. pylori. Complete regression rate after H. pylori eradication is reported at 74.5% to 94.4%. Radiotherapy results in favorable clinical long-term outcomes in patients with early-stage gastric MALT lymphoma who fail H. pylori eradication therapy and those who are H. pylori negative. Chemotherapy could be reserved for patients with metastatic or high-grade lymphoma. In gastric MALT lymphoma, patients with polypoid type on initial endoscopy had a higher likelihood of recurrence than those with diffuse infiltration or ulceration types. The depth of invasion, location of lesions, and chromosomal abnormality with t(11;18) together are predictive factors for failure to remission by H. pylori eradication.

  19. Primary esophageal mucosa-associated lymphoid tissue lymphoma diagnosed by using stacked forceps biopsy.

    PubMed

    Lee, D S; Ahn, Y C; Eom, D W; Lee, S J

    2016-10-01

    Non-Hodgkin lymphoma involving the esophagus is very rare. Only a few cases have been reported in the English literature to date, and it accounts for less than 1% of all cases of gastrointestinal lymphoma. As this malignancy manifests as a submucosal tumor, pathological diagnosis by using a simple endoscopic biopsy alone is difficult. Therefore, surgical biopsy, endoscopic mucosal resection, and endoscopic ultrasound-guided fine-needle aspiration have been used in most cases. Herein, we report a case of esophageal mucosa-associated lymphoid tissue lymphoma in a 49-year-old man, which involved the use of a stacked forceps biopsy to obtain adequate samples for pathological analysis; the use of the stacked forceps biopsy method is unlike those used in previous cases. The patient received cyclophosphamide, vincristine, and prednisolone chemotherapy; he achieved a complete response. In addition, we review the literature relevant to this case.

  20. Radiotherapy for mucosa-associated lymphoid tissue (MALT) lymphoma of the rectum: a case report.

    PubMed

    Hayakawa, Toyokazu; Nonaka, Tetsuo; Mizoguchi, Nobutaka; Hagiwara, Yasuhito; Shibata, Shino; Sakai, Rika; Nakayama, Norisuke; Yokose, Tomoyuki; Nakayama, Yuko

    2017-08-16

    Extra-nodal mucosa-associated lymphoid tissue (MALT) lymphoma is frequently involved with the upper gastrointestinal tract, but rarely involved with the rectum. We report a case of rectal MALT lymphoma treated by radiotherapy (RT) alone. A 74-year-old woman with lower abdominal pain was diagnosed with MALT lymphoma by endoscopic mucosal resection (EMR). She was diagnosed as stage IE (Ann Arbor) MALT lymphoma by diagnostic work-up and review of EMR specimens. Definitive RT was performed with curative intent, totaling 30 Gy in 15 fractions. Complete response was confirmed by colonoscopy after RT with no progression observed at 5 years. Definitive RT is effective for rectal MALT lymphoma.

  1. Structural normalization of the lymphoid tissue in asymptomatic HIV-infected patients after 48 weeks of potent antiretroviral therapy.

    PubMed

    Macías, J; Japón, M A; Leal, M; Sáez, C; Pineda, J A; Segura, D I; Ortega, J; Lissen, E

    2001-12-07

    The hallmark of HIV infection is the involution and destruction of lymphoid tissue. However, very little information exists on the effect of highly active antiretroviral therapy (HAART) on lymphoid tissue structure. To evaluate the effect of a HAART regimen after 48 weeks on the architecture and cell regeneration of tonsil lymphoid tissue in HIV-infected patients with CD4 T cell counts > or = 500/microl. From June 1997 to February 1998 all asymptomatic HIV-infected patients with CD4 T cell counts > or = 500/microl seen at our unit were offered quadruple antiretroviral therapy. Tonsil biopsies were obtained at baseline and at 48 weeks. Tonsil tissue sections were examined to evaluate structural and immunohistochemical changes by two blinded and independent pathologists. Cell numbers were counted for selected markers in T-dependent zones. Eleven patients were evaluable, six were excluded because of insufficient or inadequate sampling in at least one of the biopsies. Cellular depletion, plasma cell accumulation and prominent vessels were observed in all cases; three excluded patients with evaluable baseline biopsies showed similar tissue lesions. Follow-up biopsies demonstrated some degree of improvement in all patients. Germinal centres appeared in seven cases that were not seen at baseline. CD4 cell counts increased and CD8 cell counts decreased significantly in lymphoid tissue. An increase in CD45RA+ cells was observed; however, the proportion of CD45+Ki67+ cells did not differ between baseline and 48 weeks. This study shows an unexpected range of moderate to severe lymphoid tissue lesions in mildly immunosuppressed HIV-infected patients, which was partly restored after 48 weeks of HAART.

  2. Murine Neonates Infected with Yersinia enterocolitica Develop Rapid and Robust Proinflammatory Responses in Intestinal Lymphoid Tissues

    PubMed Central

    Siefker, David T.; Echeverry, Andrea; Brambilla, Roberta; Fukata, Masayuki; Schesser, Kurt

    2014-01-01

    Neonatal animals are generally very susceptible to infection with bacterial pathogens. However, we recently reported that neonatal mice are highly resistant to orogastric infection with Yersinia enterocolitica. Here, we show that proinflammatory responses greatly exceeding those in adults arise very rapidly in the mesenteric lymph nodes (MLN) of neonates. High-level induction of proinflammatory gene expression occurred in the neonatal MLN as early as 18 h postinfection. Marked innate phagocyte recruitment was subsequently detected at 24 h postinfection. Enzyme-linked immunosorbent spot assay (ELISPOT) analyses indicated that enhanced inflammation in neonatal MLN is contributed to, in part, by an increased frequency of proinflammatory cytokine-secreting cells. Moreover, both CD11b+ and CD11b− cell populations appeared to play a role in proinflammatory gene expression. The level of inflammation in neonatal MLN was also dependent on key bacterial components. Y. enterocolitica lacking the virulence plasmid failed to induce innate phagocyte recruitment. In contrast, tumor necrosis factor alpha (TNF-α) protein expression and neutrophil recruitment were strikingly higher in neonatal MLN after infection with a yopP-deficient strain than with wild-type Y. enterocolitica, whereas only modest increases occurred in adults. This hyperinflammatory response was associated with greater colonization of the spleen and higher mortality in neonates, while there was no difference in mortality among adults. This model highlights the dynamic levels of inflammation in the intestinal lymphoid tissues and reveals the protective (wild-type strain) versus harmful (yopP-deficient strain) consequences of inflammation in neonates. Moreover, these results reveal that the neonatal intestinal lymphoid tissues have great potential to rapidly mobilize innate components in response to infection with bacterial enteropathogens. PMID:24478090

  3. [Effects of prebiotics and probiotics on gastrointestinal tract lymphoid tissue in hiv infected patients].

    PubMed

    Feria, Manuel G; Taborda, Natalia A; Hernandez, Juan C; Rugeles, María T

    2017-02-01

    HIV infection induces alterations in almost all immune cell populations, mainly in CD4+ T cells, leading to the development of opportunistic infections. The gut-associated lymphoid tissue (GALT) constitutes the most important site for viral replication, because the main target cells, memory T-cells, reside in this tissue. It is currently known that alterations in GALT are critical during the course of the infection, as HIV-1 induces loss of tissue integrity and promotes translocation of microbial products from the intestinal lumen to the systemic circulation, leading to a persistent immune activation state and immune exhaustion. Although antiretroviral treatment decreases viral load and substantially improves the prognosis of the infection, the alterations in GALT remains, having a great impact on the ability to establish effective immune responses. This emphasizes the importance of developing new therapeutic alternatives that may promote structural and functional integrity of this tissue. In this regard, therapy with probiotics/prebiotics has beneficial effects in GALT, mainly in syndromes characterized by intestinal dysbiosis, including the HIV-1 infection. In these patients, the consumption of probiotics/prebiotics decreased microbial products in plasma and CD4+ T cell activation, increased CD4+ T cell frequency, in particular Th17, and improved the intestinal flora. In this review, the most important findings on the potential impact of the probiotics/prebiotics therapy are discussed.

  4. Histological and immunohistological investigation of the lymphoid tissue in normal and mycobacteria-affected specimens of the Rufous Hare-wallaby (Lagorchestes hirsutus)

    PubMed Central

    Young, LJ; McFarlane, R; Slender, AL; Deane, EM

    2003-01-01

    The histology of the spleen, lymph nodes, Gut-associated lymphoid tissue (GALT) and Bronchus-associated lymphoid tissue (BALT) are described for samples collected opportunistically from healthy and mycobacteria-affected specimens of the endangered marsupial Lagorchestes hirsutus, the Rufous Hare-wallaby. The structural elements, organization and distribution of T and B lymphocytes determined by immunohistological techniques using species cross-reactive antibodies in the lymph nodes, spleen and GALT of this species demonstrated lymphoid cell distributions that were consistent with other marsupial and eutherian mammals. The tissues of animals identified as acid-fast positive displayed immunopathology consistent with the responses to intracellular bacteria displayed in some eutherian mammals and included the presence of focal lesions, giant cells in the lung and lymphoid aggregations situated adjacent to blood and airway vessels. This is the first study to describe the lymphoid tissue of this rare macropod species and the first to document the tissue bed response to mycobacteria. PMID:12713272

  5. Distribution pattern of bovine viral diarrhoea virus type 1 genome in lymphoid tissues of experimentally infected sheep.

    PubMed

    Karikalan, M; Rajukumar, K; Mishra, N; Kumar, M; Kalaiyarasu, S; Rajesh, K; Gavade, V; Behera, S P; Dubey, S C

    2016-06-01

    In this study, cellular localization and the distribution pattern of BVDV genome in lymphoid tissues during the course of experimental acute BVDV-1 infection of sheep was investigated. Tonsils, mesenteric lymph nodes (MLN) and spleen were collected on 3, 6, 9, 12 and 15 days post infection (dpi) from twenty 4-month-old lambs, experimentally inoculated intra-nasally with 5 × 10(5) TCID50 of a non-cytopathic (ncp) BVDV-1 isolate, Ind-17555. Tissues collected from ten mock-infected lambs served as controls. In situ hybridization (ISH) was carried out in paraformaldehyde fixed paraffin embedded tissue sections using digoxigenin labelled riboprobe targeting 5'-UTR of BVDV-1. BVDV genome was detected at all the intervals from 3 dpi to 15 dpi in the lymphoid tissues with variations between the intervals and also amongst the infected sheep. During the early phase of acute infection, presence of viral genome was more in tonsils than MLN and spleen, whereas the distribution was higher in MLN during later stages. BVDV-1 genome positive cells included lymphocytes, macrophages, plasma cells, reticular cells and sometimes crypt epithelial cells. Genome distribution was frequently observed in the lymphoid follicles of tonsils, MLN and spleen, besides the crypt epithelium in tonsils, paracortex and medullary sinus and cords of MLN. Most abundant and widespread distribution of BVDV-1 genome was observed on 6 dpi while there was a reduction in number and intensity of positive signals by 15 dpi in most of the infected animals. This is the first attempt made to study the localisation of BVDV-1 in lymphoid tissues of acutely infected sheep by in situ hybridization. The results show that the kinetics of BVDV-1 distribution in lymphoid tissues of experimentally infected non-pregnant sheep follows almost a similar pattern to that demonstrated in BVDV infected cattle.

  6. Association of Serum CXCL13 with Intrarenal Ectopic Lymphoid Tissue Formation in Lupus Nephritis

    PubMed Central

    Chen, Wen Li; Long, Kang Xia; Zhang, Xiao

    2016-01-01

    Aims. To assess the concentrations of serum CXCL13 and intrarenal ectopic lymphoid tissue (ELT) profiles and their correlation in the patients with lupus nephritis (LN). Methods. Serum CXCL13 levels were measured using enzyme-linked immunosorbent assays (ELISA). The expression of CD3, CD20, and CD21 in renal biopsy specimens was tested using immunohistochemical methods. Results. Serum CXCL13 levels were significantly higher in the LN group than those in the SLE group without LN and also in the type III and IV LN patients than in type V LN patients. LN patients with positive CD20 expression (CD20+ LN) had a longer disease course and poorer response to combination therapy and higher serum CXCL13 levels than CD20− LN patients. Moreover, the serum CXCL13 level was positively correlated with the number of B cells/HP in the renal tissue of LN patients. The coexpression patterns of CD3, CD20, and CD21 in the renal tissue of LN patients with different WHO pathological types were significantly different. Serum CXCL13 levels were significantly higher in ELT-2 type LN patients than in 0 or 1 type LN patients. Conclusions. This study suggested that increased serum levels of CXCL13 might be involved in renal ELT formation and renal impairment process in LN. PMID:27990444

  7. CD30 ligand expression in nonmalignant and Hodgkin's disease-involved lymphoid tissues.

    PubMed Central

    Gruss, H. J.; Pinto, A.; Gloghini, A.; Wehnes, E.; Wright, B.; Boiani, N.; Aldinucci, D.; Gattei, V.; Zagonel, V.; Smith, C. A.; Kadin, M. E.; von Schilling, C.; Goodwin, R. G.; Herrmann, F.; Carbone, A.

    1996-01-01

    The CD30 ligand (CD30L) is a type II transmembrane glycoprotein of the tumor necrosis factor ligand superfamily. Recent cloning of CD30L has enabled studies to explore its function and tissue distribution. For instance, recombinant CD30L has been shown to co-stimulate T cells and to act as mitogen for Hodgkin's disease (HD)-derived cell lines. The counter-receptor for CD30L, ie, CD30, is a type I cytokine receptor that is highly expressed by activated T cells, Hodgkin and Reed-Sternberg (H-RS) cells, and anaplastic large cell lymphoma cells. In the present study, recombinant membrane-bound and soluble human CD30L were instrumental to raise a monoclonal antibody (M80) recognizing membrane-bound CD30L on transfected and native cells. With this reagent, a panel of cultured lymphoma-derived cell lines as well as primary normal, reactive, and HD-involved lymphoid tissues were examined for expression of CD30L by immunostaining and flow cytometry. In reactive lymphnodes and tonsils, CD30L was expressed by a small subset of lymphoid cells, histiocytes, and granulocytes. Higher levels of CD30L expression were noted in HD lesions among bystander cells; ie, T cells and granulocytes that surrounded H-RS cells. Native CD30L displayed at the cell surface was functionally active as shown by the ability of fixed granulocytes to interact with CD30+ cell lines. Moreover, CD30L was detectable, although to a lower staining intensity, in primary H-RS cells of all HD tissues investigated regardless of the histological subtype and the phenotype of H-RS cells (ie, CD30+/CD40+ versus CD30-/CD40+). Co-expression of CD30 and CD30L that was seen on H-RS cells of all, except the CD30- nodular lymphocyte predominant, subtypes of HD may point to the use of this pair of molecules in paracrine and/or autocrine mitogenic cell interactions. Monoclonal antibody M80 may thus represent a useful tool for studying CD30L expression on cultured cell lines and primary cells from normal, reactive, and

  8. Clusterin in human gut-associated lymphoid tissue, tonsils, and adenoids: localization to M cells and follicular dendritic cells.

    PubMed

    Verbrugghe, Phebe; Kujala, Pekka; Waelput, Wim; Peters, Peter J; Cuvelier, Claude A

    2008-03-01

    The follicle-associated epithelium (FAE) overlying the follicles of mucosa-associated lymphoid tissue is a key player in the initiation of mucosal immune responses. We recently reported strong clusterin expression in the FAE of murine Peyer's patches. In this study, we examined the expression of clusterin in the human gut-associated lymphoid tissue (GALT) and Waldeyer's ring. Immunohistochemistry for clusterin in human Peyer's patches, appendix and colon lymphoid follicles revealed expression in M cells and in follicular dendritic cells (FDCs). Using cryo-immunogold electron microscopy in Peyer's patches, we observed cytosolic immunoreactivity in M cells and labeling in the ER/Golgi biosynthetic pathway in FDCs. In palatine tonsils and adenoids, we demonstrated clusterin expression in germinal centers and in the lymphoepithelium in the crypts where M cells are localized. In conclusion, clusterin is expressed in M cells and follicular dendritic cells at inductive sites of human mucosa-associated lymphoid tissue suggesting a role for this protein in innate immune responses. Moreover, the use of clusterin as a human M cell marker could prove to be a valuable tool in future M cell research.

  9. Vancomycin pre-treatment impairs tissue healing in experimental colitis: Importance of innate lymphoid cells.

    PubMed

    Zhao, Di; Cai, Chenwen; Zheng, Qing; Jin, Shuang; Song, Dongjuan; Shen, Jun; Ran, Zhihua

    2017-01-29

    The interplay between luminal microbes and innate immunity during colonic epithelial repair has been well noted. At the same time, antibiotic has widely been used during flare-ups of ulcerative colitis. The possible effects of luminal microbiota disruption caused by antibiotics usage on epithelial repairing have been scarcely discussed. Innate lymphoid cells (ILCs) embedded in the lamina propria can be modulated by gut microbes, resulting in altered colonic IL-22/pSTAT3 levels, which is considered a prominent molecular axis in tissue repairing after epithelium damage. This study aimed to investigate whether antibiotics could interfere with ILCs-dependent tissue repair. Dextran sodium sulfate (DSS)-induced colitis was established in mice pre-treated with reagent of different antibiotic spectrum. Both morphological and molecular markers of tissue repair after DSS cessation were detected. ILCs population and function status were also recorded. Further attention was paid to the response of dendritic cells after antibiotics treatment, which were claimed to regulate colonic ILC3s in an IL-23 dependent way. Using of vancomycin resulted in delayed tissue repairing after experimental colitis. Both colonic IL-22/pSTAT3 axis and ILC3 population were found decreased in this situation. Vancomycin treatment diminished the upstream IL-23 and producer dendritic cell population. The reduced dendritic cell number may due to inadequate chemokines and colony-stimulating factors supply. Presence of vancomycin-sensitive microbiota is required for the maturation of ILC3-activating dendritic cells hence maintain the sufficient IL-22/pSTAT3 level in the colon during tissue healing. Manipulation of colonic microbiota may help achieve colonic mucosal healing post inflammation and injury. Copyright © 2016. Published by Elsevier Inc.

  10. Marginal reticular cells: a stromal subset directly descended from the lymphoid tissue organizer

    PubMed Central

    Katakai, Tomoya

    2012-01-01

    The architecture of secondary lymphoid organs (SLOs) is supported by several non-hematopoietic stromal cells. Currently it is established that two distinct stromal subsets, follicular dendritic cells and fibroblastic reticular cells, play crucial roles in the formation of tissue compartments within SLOs, i.e., the follicle and T zone, respectively. Although stromal cells in the anlagen are essential for SLO development, the relationship between these primordial cells and the subsets in adulthood remains poorly understood. In addition, the roles of stromal cells in the entry of antigens into the compartments through some tissue structures peculiar to SLOs remain unclear. A recently identified stromal subset, marginal reticular cells (MRCs), covers the margin of SLOs that are primarily located in the outer edge of follicles and construct a unique reticulum. MRCs are closely associated with specialized endothelial or epithelial structures for antigen transport. The similarities in marker expression profiles and successive localization during development suggest that MRCs directly descend from organizer stromal cells in the anlagen. Therefore, MRCs are thought to be a crucial stromal component for the organization and function of SLOs. PMID:22807928

  11. Innate lymphoid type 2 cells sustain visceral adipose tissue eosinophils and alternatively activated macrophages

    PubMed Central

    Molofsky, Ari B.; Nussbaum, Jesse C.; Liang, Hong-Erh; Van Dyken, Steven J.; Cheng, Laurence E.; Mohapatra, Alexander; Chawla, Ajay

    2013-01-01

    Eosinophils in visceral adipose tissue (VAT) have been implicated in metabolic homeostasis and the maintenance of alternatively activated macrophages (AAMs). The absence of eosinophils can lead to adiposity and systemic insulin resistance in experimental animals, but what maintains eosinophils in adipose tissue is unknown. We show that interleukin-5 (IL-5) deficiency profoundly impairs VAT eosinophil accumulation and results in increased adiposity and insulin resistance when animals are placed on a high-fat diet. Innate lymphoid type 2 cells (ILC2s) are resident in VAT and are the major source of IL-5 and IL-13, which promote the accumulation of eosinophils and AAM. Deletion of ILC2s causes significant reductions in VAT eosinophils and AAMs, and also impairs the expansion of VAT eosinophils after infection with Nippostrongylus brasiliensis, an intestinal parasite associated with increased adipose ILC2 cytokine production and enhanced insulin sensitivity. Further, IL-33, a cytokine previously shown to promote cytokine production by ILC2s, leads to rapid ILC2-dependent increases in VAT eosinophils and AAMs. Thus, ILC2s are resident in VAT and promote eosinophils and AAM implicated in metabolic homeostasis, and this axis is enhanced during Th2-associated immune stimulation. PMID:23420878

  12. IL-33 activates eosinophils of visceral adipose tissue both directly and via innate lymphoid cells.

    PubMed

    Hashiguchi, Masaaki; Kashiwakura, Yuji; Kojima, Hidefumi; Kobayashi, Ayano; Kanno, Yumiko; Kobata, Tetsuji

    2015-03-01

    Eosinophils are multifunctional leukocytes involved in allergic reactions as well as adipose tissue regulation. IL-5 is required for eosinophil survival; however, the in vivo mechanisms of eosinophil regulation are not fully understood. A tg mouse model with il5 promoter-driven EGFP expression was established for detecting the IL-5-producing cells in vivo. Il5-egfp tg mice expressed high levels of EGFP in gonadal adipose tissue (GAT) cells. EGFP(+) cells in GAT were mainly group 2 innate lymphoid cells (ILCs). IL-33 preferentially expanded EGFP(+) cells and eosinophils in GAT in vivo. EGFP(+) ILCs were found to upregulate prg2 mRNA expression in GAT eosinophils. These results demonstrate that ILCs activate eosinophils in GAT. The blockage of IL-33Rα, on the other hand, did not impair EGFP(+) ILC numbers but did impair eosinophil numbers in vivo. GAT eosinophils expressed IL-33Rα and IL-33 expanded eosinophil numbers in CD90(+) cell-depleted mice. IL-33 was further observed to induce the expression of retnla and epx mRNA in eosinophils. These findings demonstrate that IL-33 directly activates eosinophils in GAT, and together with our other findings described above, our findings show that IL-33 has dual pathways via which it activates eosinophils in vivo: a direct activation pathway and a group 2 ILC-mediated pathway.

  13. Characterisation of Regulatory T Cells in Nasal Associated Lymphoid Tissue in Children: Relationships with Pneumococcal Colonization

    PubMed Central

    Zhang, Qibo; Leong, Samuel C.; McNamara, Paul S.; Mubarak, Ayman; Malley, Richard; Finn, Adam

    2011-01-01

    Regulatory T cells (Treg) diminish immune responses to microbial infection, which may contribute to preventing inflammation-related local tissue damage and autoimmunity but may also contribute to chronicity of infection. Nasopharyngeal carriage of pneumococcus is common in young children and can persist for long periods but it is unknown whether the presence of Treg in the nasopharynx contributes to this persistence. We have investigated the numbers and activities of Foxp3+Treg in adenoidal tissues and their association with pneumococcal carriage in children. Expression of Treg cell-related markers including Foxp3, CD25, CD39, CD127 and CLTA4 were analysed by flow-cytometry in adenoidal mononuclear cells (MNC) and PBMC from children. Unfractionated MNC or Treg-depleted MNC were stimulated with a pneumococcal whole cell antigen (WCA) and T cell proliferation measured. Cytokine production by MNC was measured using a cytometric bead array. Higher numbers of CD25highFoxp3high Treg expressing higher CD39 and CTLA4 were found in adenoidal MNC than in PBMC. Children with pneumococcus positive nasopharyngeal cultures had higher proportions of Treg and expressed higher levels of CD39 and CTLA-4 than those who were culture negative (−). WCA induced adenoidal Treg proliferation which produce IL10 but not IL17, and CD4 T cell proliferation in Treg-depleted MNC was greater in pneumococcal culture positive than negative children. Significant numbers of Treg with an effector/memory phenotype which possess a potent inhibitory effect, exist in adenoidal tissue. The association of pneumococcal carriage with an increased frequency of adenoidal Treg suggests that Treg in nasal-associated lymphoid tissue (NALT) may contribute to the persistence of pneumococcus in children. Further studies to determine what component and mechanisms are involved in the promotion of Treg in NALT may lead to novel therapeutic or vaccination strategy against upper respiratory infection. PMID:21852948

  14. Transcriptional profiling of peripheral lymphoid tissue reveals genes and networks linked to SSBP/1 scrapie pathology in sheep.

    PubMed

    Gossner, Anton; Roupaka, Sofia; Foster, Jim; Hunter, Nora; Hopkins, John

    2011-12-15

    Transmissible spongiform encephalopathies (TSEs) are slow and progressive neurodegenerative diseases of humans and animals. The major target organ for all TSEs is the brain but some TSE agents are associated with prior accumulation within the peripheral lymphoid system. Many studies have examined the effects of scrapie infection on the expression of central nervous system (CNS) genes, but this study examines the progression of scrapie pathology in the peripheral lymphoid system and how scrapie infection affects the transcriptome of the lymph nodes and spleen. Infection of sheep with SSBP/1 scrapie resulted in PrP(Sc) deposition in the draining prescapular lymph node (PSLN) by 25 days post infection (dpi) in VRQ/VRQ genotype sheep and 75 dpi in tonsils and spleen. Progression of PrP(Sc) deposition in VRQ/ARR animals was 25 dpi later in the PSLN and 250 dpi later in spleen. Microarray analysis of 75 dpi tissues from VRQ/VRQ sheep identified 52 genes in PSLN and 37 genes in spleen cells that showed significant difference (P ≤ 0.05) between scrapie-infected and mock-infected animals. Transcriptional pathway analysis highlighted immunological disease, cell death and neurological disease as the biological pathways associated with scrapie pathogenesis in the peripheral lymphoid system. PrP(Sc) accumulation of lymphoid tissue resulted in the repression of genes linked to inflammation and oxidative stress, and the up-regulation of genes related to apoptosis.

  15. Innate production of T(H)2 cytokines by adipose tissue-associated c-Kit(+)Sca-1(+) lymphoid cells.

    PubMed

    Moro, Kazuyo; Yamada, Taketo; Tanabe, Masanobu; Takeuchi, Tsutomu; Ikawa, Tomokatsu; Kawamoto, Hiroshi; Furusawa, Jun-Ichi; Ohtani, Masashi; Fujii, Hideki; Koyasu, Shigeo

    2010-01-28

    Innate immune responses are important in combating various microbes during the early phases of infection. Natural killer (NK) cells are innate lymphocytes that, unlike T and B lymphocytes, do not express antigen receptors but rapidly exhibit cytotoxic activities against virus-infected cells and produce various cytokines. Here we report a new type of innate lymphocyte present in a novel lymphoid structure associated with adipose tissues in the peritoneal cavity. These cells do not express lineage (Lin) markers but do express c-Kit, Sca-1 (also known as Ly6a), IL7R and IL33R. Similar lymphoid clusters were found in both human and mouse mesentery and we term this tissue 'FALC' (fat-associated lymphoid cluster). FALC Lin(-)c-Kit(+)Sca-1(+) cells are distinct from lymphoid progenitors and lymphoid tissue inducer cells. These cells proliferate in response to IL2 and produce large amounts of T(H)2 cytokines such as IL5, IL6 and IL13. IL5 and IL6 regulate B-cell antibody production and self-renewal of B1 cells. Indeed, FALC Lin(-)c-Kit(+)Sca-1(+) cells support the self-renewal of B1 cells and enhance IgA production. IL5 and IL13 mediate allergic inflammation and protection against helminth infection. After helminth infection and in response to IL33, FALC Lin(-)c-Kit(+)Sca-1(+) cells produce large amounts of IL13, which leads to goblet cell hyperplasia-a critical step for helminth expulsion. In mice devoid of FALC Lin(-)c-Kit(+)Sca-1(+) cells, such goblet cell hyperplasia was not induced. Thus, FALC Lin(-)c-Kit(+)Sca-1(+) cells are T(H)2-type innate lymphocytes, and we propose that these cells be called 'natural helper cells'.

  16. Upper Airway Lymphoid Tissue Size in Children With Sickle Cell Disease

    PubMed Central

    Strauss, Temima; Sin, Sanghun; Marcus, Carole L.; Mason, Thornton B. A.; McDonough, Joseph M.; Allen, Julian L.; Caboot, Jason B.; Bowdre, Cheryl Y.; Jawad, Abbas F.; Smith-Whitley, Kim; Ohene-Frempong, Kwaku; Pack, Allan I.

    2012-01-01

    Background: The prevalence of obstructive sleep apnea syndrome (OSAS) is higher in children with sickle cell disease (SCD) as compared with the general pediatric population. It has been speculated that overgrowth of the adenoid and tonsils is an important contributor. Methods: The current study used MRI to evaluate such an association. We studied 36 subjects with SCD (aged 6.9 ± 4.3 years) and 36 control subjects (aged 6.6 ± 3.4 years). Results: Compared with control subjects, children with SCD had a significantly smaller upper airway (2.8 ± 1.2 cm3 vs 3.7 ± 1.6 cm3, P < .01), and significantly larger adenoid (8.4 ± 4.1 cm3 vs 6.0 ± 2.2 cm3, P < .01), tonsils (7.0 ± 4.3 cm3 vs 5.1 ± 1.9 cm3, P < .01), retropharyngeal nodes (3.0 ± 1.9 cm3 vs 2.2 ± 0.9 cm3, P < .05), and deep cervical nodes (15.7 ± 5.7 cm3 vs 12.7 ± 4.0 cm3, P < .05). Polysomnography showed that 19.4% (seven of 36) of children with SCD had OSAS compared with 0% (zero of 20) of control subjects (P < .05) and that in children with SCD the apnea-hypopnea index correlated positively with upper airway lymphoid tissues size (r = 0.57, P < 001). In addition, children with SCD had lower arterial oxygen saturation nadir (84.3% ± 12.3% vs 91.2% ± 4.2%, P < .05), increased peak end-tidal CO2 (53.4 ± 8.5 mm Hg vs 42.3 ± 5.3 mm Hg, P < .001), and increased arousals (13.7 ± 4.7 events/h vs 10.8 ± 3.8 events/h, P < .05). Conclusions: Children with SCD have reduced upper airway size due to overgrowth of the surrounding lymphoid tissues, which may explain their predisposition to OSAS. PMID:22241762

  17. Impact of tobacco smoke on interleukin-16 protein in human airways, lymphoid tissue and T lymphocytes

    PubMed Central

    ANDERSSON, A; QVARFORDT, I; LAAN, M; SJÖSTRAND, M; MALMHÄLL, C; RIISE, G C; CARDELL, L-O; LINDÉN, A

    2004-01-01

    CD4+ and CD8+ lymphocytes are mobilized in severe chronic obstructive pulmonary disease (COPD) and the CD8+ cytokine interleukin (IL)-16 is believed to be important in regulating the recruitment and activity of CD4+ lymphocytes. In the current study, we examined whether tobacco smoke exerts an impact not only on IL-16 in the lower airways but also in CD4+ or CD8+ lymphocytes or in lymphoid tissue. The concentration of IL-16 protein was measured by enzyme-linked immunosorbent assay (ELISA) in concentrated bronchoalveolar lavage fluid (BALF) collected from 33 smokers with chronic bronchitis (CB), eight asymptomatic smokers (AS) and seven healthy never-smokers (NS). The concentrations of IL-16 and soluble IL-2 receptor alpha (sIL-2Rα) protein were also measured in conditioned medium from human blood CD4+ and CD8+ lymphocytes stimulated with tobacco smoke extract (TSE) in vitro. IL-16 mRNA was assessed in vitro as well, using reverse transcription–polymerase chain reaction (RT-PCR). Finally, the intracellular immunoreactivity for IL-16 protein (IL-16IR) was assessed in six matched pairs of palatine tonsils from smokers and non-smokers. BALF IL-16 was higher in CB and AS than in NS. TSE substantially increased the concentration of IL-16 but not sIL-2Rα in conditioned medium from CD4+ and CD8+ lymphocytes. There was no corresponding effect on IL-16 mRNA. IL-16IR in tonsils was lower in smokers than in non-smokers. The current findings demonstrate that tobacco smoke exerts a wide impact on the CD8+ cytokine IL-16, in the airway lumen, in blood CD4+ and CD8+ lymphocytes and in lymphoid tissue. The effect on IL-16 release may be selective for preformed IL-16 in CD4+ lymphocytes. New clinical studies are required to evaluate whether tobacco smoke mobilizes T lymphocytes via IL-16 in the lower airways and whether this mechanism can be targeted in COPD. PMID:15373908

  18. Expression of duck CCL19 and CCL21 and CCR7 receptor in lymphoid and influenza-infected tissues

    PubMed Central

    Canepa, Ximena Fleming; Brusnyk, Craig; Aldridge, Jerry R.; Ross, Katherine L.; Moon, Debra; Wang, Dong; Xia, Jianguo; Barber, Megan R. W.; Webster, Robert G.; Magor, Katharine E.

    2011-01-01

    Ducks are the natural host and reservoir of influenza viruses. We are interested in their immune responses to these viruses, to understand host-pathogen interactions and to develop effective agricultural vaccines. We identified duck homologues of the chemokines CCL19 and CCL21 and cloned their cognate receptor, CCR7. Conservation of key features, and expression in lymphoid tissues suggests that these chemokines are the direct orthologues of their mammalian counterparts. Mammalian CCL19 and CCL21 are responsible for the homing of dendritic cells and naïve lymphocytes to secondary lymphoid tissues. The contribution of local tertiary lymphoid tissues may be important during influenza infection in ducks. Consistent with leukocyte recruitment, CCL19 and CCL21 transcripts are abundant in lung tissues at 1 day post-infection with highly pathogenic avian influenza A/Vietnam/1203/04 (H5N1) (VN1203). In contrast, expression in lung or intestine tissues infected with low pathogenic A/mallard/BC/500/05 (H5N2) (BC500) is not significant. Recruitment and aggregation of leukocytes is visible in the vicinity of major airways 3 days after infection with VN1203. Chemokine gene expression may serve as a useful marker to evaluate duck immune responses to natural infections and vaccine strains. PMID:21704378

  19. Eosinophil-nerve interactions and neuronal plasticity in rat gut associated lymphoid tissue (GALT) in response to enteric parasitism.

    PubMed

    O'Brien, L M; Fitzpatrick, E; Baird, A W; Campion, D P

    2008-06-15

    Intestinal lymphoid tissues and Peyer's patches (PP) are innervated sites of immune surveillance in the gastrointestinal tract. Following infection with F. hepatica, neuronal hyperplasia and significantly increased eosinophil and mast cell trafficking to colonic PP sites were evident in rat tissues. Nerve-eosinophil associations were significantly elevated in infected colon and colonic PP, as were colonic tissue levels of the circulatory recruitment factors IL-5 and eotaxin. Increased immunoreactivity for neuronal plasticity markers GAP-43 and neural cell adhesion molecule (NCAM) was also found in infected tissues. Such neuronal alterations in the PP during enteric parasitism may have functional consequences on particular or pathogen uptake.

  20. Disease-Associated Prion Protein in Neural and Lymphoid Tissues of Mink (Mustela vison) Inoculated with Transmissible Mink Encephalopathy

    PubMed Central

    Schneider, D. A.; Harrington, R. D.; Zhuang, D.; Yan, H.; Truscott, T. C.; Dassanayake, R. P.; O'Rourke, K. I.

    2012-01-01

    Summary Transmissible spongiform encephalopathies (TSEs) are diagnosed by immunodetection of disease-associated prion protein (PrPd). The distribution of PrPd within the body varies with the time-course of infection and between species, during interspecies transmission, as well as with prion strain. Mink are susceptible to a form of TSE known as transmissible mink encephalopathy (TME), presumed to arise due to consumption of feed contaminated with a single prion strain of ruminant origin. After extended passage of TME isolates in hamsters, two strains emerge, HY and DY, each of which is associated with unique structural isoforms of PrPTME and of which only the HY strain is associated with accumulation of PrPTME in lymphoid tissues. Information on the structural nature and lymphoid accumulation of PrPTME in mink is limited. In this study, 13 mink were challenged by intracerebral inoculation using late passage TME inoculum after which brain and lymphoid tissues were collected at preclinical and clinical time points. The distribution and molecular nature of PrPTME was investigated by techniques including blotting of paraffin wax-embedded tissue and epitope mapping by western blotting. PrPTME was detected readily in the brain and retropharyngeal lymph node during preclinical infection with delayed progression of accumulation within other lymphoid tissues. For comparison, three mink were inoculated by the oral route and examined during clinical disease. Accumulation of PrPTME in these mink was greater and more widespread, including follicles of rectoanal mucosa-associated lymphoid tissue. Western blot analyses revealed that PrPTME accumulating in the brain of mink is structurally most similar to that accumulating in the brain of hamsters infected with the DY strain. Collectively, the results of extended passage in mink are consistent with the presence of only a single strain of TME, the DY strain, capable of inducing accumulation of PrPTME in the lymphoid tissues of

  1. Characterisation of inorganic microparticles in pigment cells of human gut associated lymphoid tissue.

    PubMed Central

    Powell, J J; Ainley, C C; Harvey, R S; Mason, I M; Kendall, M D; Sankey, E A; Dhillon, A P; Thompson, R P

    1996-01-01

    Macrophages at the base of human gut associated lymphoid tissue (GALT), become loaded early in life with dark granular pigment that is rich in aluminium, silicon, and titanium. The molecular characteristics, intracellular distribution, and source of this pigment is described. Laser scanning and electron microscopy showed that pigmented macrophages were often closely related to collagen fibres and plasma cells in GALT of both small and large intestine and contained numerous phagolysosomes, previously described as granules, that are rich in electron dense submicron sized particles. Morphological assessment, x ray microanalysis, and image electron energy loss spectroscopy showed three distinct types of microparticle: type I - spheres of titanium dioxide, 100-200 nm diameter, characterised as the synthetic food-additive polymorph anatase; type II - aluminosilicates, < 100-400 nm in length, generally of flaky appearance, often with adsorbed surface iron, and mostly characteristic of the natural clay mineral kaolinite; and type III - mixed environmental silicates without aluminium, 100-700 nm in length and of variable morphology. Thus, this cellular pigment that is partly derived from food additives and partly from the environment is composed of inert inorganic microparticles and loaded into phagolysosomes of macrophages within the GALT of all human subjects. These observations suggest that the pathogenicity of this pigment should be further investigated since, in susceptible individuals, the same intracellular distribution of these three types of submicron particle causes chronic latent granulomatous inflammation. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 7 PMID:8675092

  2. Efficient SIVcpz replication in human lymphoid tissue requires viral matrix protein adaptation

    PubMed Central

    Bibollet-Ruche, Frederic; Heigele, Anke; Keele, Brandon F.; Easlick, Juliet L.; Decker, Julie M.; Takehisa, Jun; Learn, Gerald; Sharp, Paul M.; Hahn, Beatrice H.; Kirchhoff, Frank

    2012-01-01

    SIVs infecting wild-living apes in west central Africa have crossed the species barrier to humans on at least four different occasions, one of which spawned the AIDS pandemic. Although the chimpanzee precursor of pandemic HIV-1 strains must have been able to infect humans, the capacity of SIVcpz strains to replicate in human lymphoid tissues (HLTs) is not known. Here, we show that SIVcpz strains from two chimpanzee subspecies are capable of replicating in human tonsillary explant cultures, albeit only at low titers. However, SIVcpz replication in HLT was significantly improved after introduction of a previously identified human-specific adaptation at position 30 in the viral Gag matrix protein. An Arg or Lys at this position significantly increased SIVcpz replication in HLT, while the same mutation reduced viral replication in chimpanzee-derived CD4+ T cells. Thus, naturally occurring SIVcpz strains are capable of infecting HLTs, the major site of HIV-1 replication in vivo. However, efficient replication requires the acquisition of a host-specific adaptation in the viral matrix protein. These results identify Gag matrix as a major determinant of SIVcpz replication fitness in humans and suggest a critical role in the emergence of HIV/AIDS. PMID:22505456

  3. Crystal structure of the mucosa-associated lymphoid tissue lymphoma translocation 1 (MALT1) paracaspase region.

    PubMed

    Yu, Jong W; Jeffrey, Philip D; Ha, Jun Yong; Yang, Xiaolu; Shi, Yigong

    2011-12-27

    The mucosa-associated lymphoid tissue lymphoma translocation 1 (MALT1) paracaspase, a key component of the Carma1/Bcl10/MALT1 signalosome, is critical for NF-κB signaling in multiple contexts. MALT1 is thought to function as a scaffold and protease to promote signaling; however, the biochemical and structural basis of paracaspase action remains largely unknown. Here we report the 1.75-Å resolution crystal structure of the MALT1 paracaspase region, which contains the paracaspase domain and an ensuing Ig-like domain. The paracaspase and the Ig domains appear as a single folding unit and interact with each other through extensive van der Waals contacts and hydrogen bonds. The paracaspase domain adopts a fold that is nearly identical to that of classic caspases and homodimerizes similarly to form an active protease. Unlike caspases, the active and mature form of the paracaspase domain remains a single uncleaved polypeptide and specifically recognizes the bound peptide inhibitor Val-Arg-Pro-Arg. In particular, the carboxyl-terminal amino acid Arg of the inhibitor is coordinated by three highly conserved acidic residues. This structure serves as an important framework for deciphering the function and mechanism of paracaspases exemplified by MALT1.

  4. Dock10 regulates CD23 expression and sustains B-cell lymphopoiesis in secondary lymphoid tissue.

    PubMed

    García-Serna, Azahara-María; Alcaraz-García, María-José; Ruiz-Lafuente, Natalia; Sebastián-Ruiz, Silvia; Martínez, Carlos-Manuel; Moya-Quiles, María-Rosa; Minguela, Alfredo; García-Alonso, Ana-María; Martín-Orozco, Elena; Parrado, Antonio

    2016-12-01

    Dock10, a guanine nucleotide exchange factor for the Rho GTPases Rac1 and Cdc42, affects cell morphology, membrane protrusive activity, and cell movement. Dock10 is prominently expressed in lymphoid tissue and upregulated by IL-4 in B cells. To investigate the physiological role of Dock10, WT mice and Dock10 KO mice were used. KO mice showed decreased numbers of B cells in spleen, both follicular B cells and marginal zone B cells, and in peripheral blood, but not in bone marrow. The antiapoptotic effect of IL-4 in vitro, the migratory response to CXCL13 or CCL21 in vitro, and the whole genome expression profile were intact in spleen B cells from KO mice. CD23, the low-affinity receptor for immunoglobulin E, was overexpressed on follicular B cells from KO mice, suggesting that Dock10 negatively regulates membrane CD23 expression. Negative regulation of CD23 expression by Dock10 could play a role in B cell maturation and function.

  5. Primary hepatic extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type

    PubMed Central

    Dong, Shuilin; Chen, Lin; Chen, Yifa; Chen, Xiaoping

    2017-01-01

    Abstract Rationale: Primary hepatic mucosa-associated lymphoid tissue (MALT) lymphoma is an extremely rare disease. To the best of our knowledge, only 67 cases had been reported in 39 English literatures to date. The aim of this study was to add a new case of this disease to the literature and to review the current literature. Patient concerns: A 50-year-old man was incidentally identified with a solitary mass of 5 cm in diameter in the left lobe of the liver. Diagnoses: Based on the results of imaging studies, intrahepatic cholangiocellular carcinoma was suspected, and then surgery was performed. Microscopic findings showed that the tumor was a hepatic MALT lymphoma, and immunohistochemical analysis revealed that the lymphoma cells were CD20+, CD79a+, BCL-2+, CD3−, and CD5−. Interventions: The patient received rituximab after surgery. Outcomes: He was free of disease for 13 months at the time of this report. Lessons: Since previously published case reports and our case described nonspecific clinical features of this rare disease, it was usually misdiagnosed before histological confirmation and surgery resection may be a good choice for both diagnosis and local therapy. PMID:28353562

  6. Mucosa-associated lymphoid tissue lymphoma of the esophagus: case report and review of the literature.

    PubMed

    Miyazaki, Tatsuya; Kato, Hiroyuki; Masuda, Norihiro; Nakajima, Masanobu; Manda, Ryokuhei; Fukuchi, Minoru; Tsukada, Katsuhiko; Kojima, Masaru; Nakajima, Takashi; Kuwano, Hiroyuki

    2004-01-01

    We report the histomorphologic and immunohistochemical features of another case of mucosa-associated lymphoid tissue (MALT) lymphoma arising from the esophagus and discuss the problems of differential diagnosis. The patient was a 49-year-old man, who had no gastrointestinal symptoms. On endoscopy, a smooth-surfaced, semibulbous lesion was found 36 cm from the incisors. We performed radical resection of this submucosal tumor with video-assisted thoracoscopic surgery for the purpose of diagnosis and treatment. The immunophenotype of the centrocyte-like-cells was CD20+, BCL2+, CD5-, CD10-, CD23- CD45RO- and cyclin D1-. Diffuse immunostaining of bcl-2 was detected in the nuclei of the tumor cells without lymph follicles. Southern blotting analyses of the IgH gene detected a single dominant band indicative of a clonal IgH rearrangement. From the pathological, immunohistochemical, and molecular biological features we concluded that the tumor was a MALT lymphoma. Only three cases of primary esophageal MALT lymphoma have been reported to date. On the basis of the present case and the three previously reported cases, we suggest that MALT lymphoma of the esophagus is usually an elevated type. The spectrum of sites in which gastrointestinal MALT lymphoma occurs should be expanded to include the esophagus.

  7. Development of T Lymphocytes in the Nasal-associated Lymphoid Tissue (NALT) from Growing Wistar Rats

    PubMed Central

    Sosa, Gustavo A.

    2004-01-01

    The aim of the present report was to study the development of several T-lymphocyte subsets in the nasal-associated lymphoid tissue (NALT) of growing Wistar rats. CD5+ and CD4+ lymphocytes gradually increased with age. A predominance of CD8α+ over CD4+ T cells was found from 7 to 45 days but from 45 to 60 days of age T helper cells outnumbered the cytotoxic subpopulation. The majority of CD8+ T lymphocytes expressed the heterodimeric isoform. The most relevant findings by immunohistochemistry are: (1) the predominance of TCRγδ+ and CD8α+ cells at 7 days postpartum over all the other T-cell subpopulations; and (2) that TCRγβ+ outnumbered TCRαβ+ T cells from 7 to 45 days postpartum whereas αβ T cells predominated in 45- and 60-day-old rats. Besides, cytometric studies have shown that the percentages of TCRγ+, CD8+, as well as the population coexpressing both phenotypes (TCRγδ+CD8α+), were significantly higher in rats at 7 days postpartum when compared to 60 day-old rats. In the present study, the finding of a high number of γδ+ and CD8+ T cells early in NALT development may indicate the importance of these subpopulations in the protection of the nasal mucosa in suckling and weaning Wistar rats. PMID:15154609

  8. Cancer Immunosurveillance by Tissue-resident Innate Lymphoid Cells and Innate-like T Cells

    PubMed Central

    Dadi, Saïda; Chhangawala, Sagar; Whitlock, Benjamin M.; Franklin, Ruth A.; Luo, Chong T.; Oh, Soyoung A.; Toure, Ahmed; Pritykin, Yuri; Huse, Morgan; Leslie, Christina S.; Li, Ming O.

    2016-01-01

    Summary Malignancy can be suppressed by the immune system in a process termed immunosurveillance. However, to what extent immunosurveillance occurs in spontaneous cancers and the composition of participating cell types remain obscure. Here we show that cell transformation triggers a tissue-resident lymphocyte response in oncogene-induced murine cancer models. Non-circulating cytotoxic lymphocytes, derived from innate, TCRαβ and TCRγδ lineages, expand in early tumors. Characterized by high expression of NK1.1, CD49a and CD103, these cells share a gene expression signature distinct from those of conventional NK cells, T cells and invariant NKT cells. Generation of these lymphocytes is dependent on the cytokine IL-15, but not the transcription factor Nfil3 that is required for the differentiation of tumor-infiltrating NK cells, and IL-15, but not Nfil3, deficiency results in accelerated tumor growth. These findings reveal a tumor-elicited immunosurveillance mechanism that engages unconventional type 1-like innate lymphoid cells and type 1 innate-like T cells. PMID:26806130

  9. Mucosa-Associated Lymphoid-Tissue Lymphoma of the Cecum and Rectum: A Case Report

    PubMed Central

    Nam, Myung Jin; Park, Sung Chan; Hong, Chang Won; Han, Kyung Su; Sohn, Dae Kyung; Park, Weon Seo; Chang, Hee Jin; Oh, Jae Hwan

    2017-01-01

    A colonic mucosa-associated lymphoid-tissue (MALT) lymphoma is relatively rare compared to lymphomas of the stomach or small intestine. We present a case of a MALT lymphoma in the cecum and rectum found during screening colonoscopy. A 54-year-old female, who had undergone right-breast-conserving surgery with axillary dissection due to an invasive ductal carcinoma and a left-breast excisional biopsy due to microcalcification following adjuvant chemoradiation therapy 3 years earlier, was found to have 3-mm-sized smooth elevated lesions in both the cecum and rectum. No pathologic lesion or lymphadenopathy was found at any other site, but chronic gastritis negative for Helicobacter pylori infection was found. The polyps were removed by using an endoscopic biopsy and revealed an extra nodal marginal zone B-cell MALT lymphoma, showing positive for CD3 and CD20 by immunohistochemical staining. The patient underwent close observation without any additional treatment and has shown no evidence of recurrence as of her last visit. PMID:28289662

  10. Gastric B-cell mucosa associated lymphoid tissue lymphoma: a clinicopathological study in 56 patients.

    PubMed Central

    Castrillo, J M; Montalban, C; Obeso, G; Piris, M A; Rivas, M C

    1992-01-01

    Clinico-pathological features of 56 patients with primary gastric lymphoma were evaluated retrospectively. All cases were regraded according to a classification of Isaacson et al into high grade and low grade B-cell mucosa associated lymphoid tissue lymphoma. A third group of mixed grade was recognised in 11 patients with low grade who also had occasional areas of high grade. Low grade and mixed grade patients had a 100% actuarial survival at 156 months, which was significantly better (p < 0.01) than that of 52% for patients with high grade disease. Different treatment methods--surgery, chemotherapy, or a combination of both--did not significantly affect survival. Low grade tumours occurred mainly in men with a history of several years, and who presented with non-specific gastric symptoms without remarkable exploratory or laboratory findings: most patients were in stage IE-IIE and achieved remission and cure. High grade can have a shorter history, systemic symptoms, abnormal exploratory and laboratory findings, gastric tumour masses, stage IV disease, and a worse outcome. The only significant prognostic factors for survival were the type of lymphoma and stage IV disease. These findings support the Isaacson classification system which separates two extreme groups of gastric lymphomas with different morphology, behaviour, and outcome. The presence of limited areas of high grade in a specimen showing low grade does not change the outcome but suggests that primary gastric lymphoma forms a continuum between these extreme types. PMID:1446850

  11. Heterogeneous fibroblasts underlie age-dependent tertiary lymphoid tissues in the kidney

    PubMed Central

    Sato, Yuki; Mii, Akiko; Hamazaki, Yoko; Fujita, Harumi; Nakata, Hirosuke; Masuda, Kyoko; Nishiyama, Shingo; Shibuya, Shinsuke; Haga, Hironori; Ogawa, Osamu; Shimizu, Akira; Narumiya, Shuh; Kaisho, Tsuneyasu; Arita, Makoto; Yanagisawa, Masashi; Sharma, Kumar; Minato, Nagahiro; Kawamoto, Hiroshi

    2016-01-01

    Acute kidney injury (AKI) is a common clinical condition defined as a rapid decline in kidney function. AKI is a global health burden, estimated to cause 2 million deaths annually worldwide. Unlike AKI in the young, which is reversible, AKI in the elderly often leads to end-stage renal disease, and the mechanism that prevents kidney repair in the elderly is unclear. Here we demonstrate that aged but not young mice developed multiple tertiary lymphoid tissues (TLTs) in the kidney after AKI. TLT size was associated with impaired renal function and increased expression of proinflammatory cytokines and homeostatic chemokines, indicating a possible contribution of TLTs to sustained inflammation after injury. Notably, resident fibroblasts from a single lineage diversified into p75 neurotrophin receptor+ (p75NTR+) fibroblasts and homeostatic chemokine–producing fibroblasts inside TLTs, and retinoic acid–producing fibroblasts around TLTs. Deletion of CD4+ cells as well as late administration of dexamethasone abolished TLTs and improved renal outcomes. Importantly, aged but not young human kidneys also formed TLTs that had cellular and molecular components similar to those of mouse TLTs. Therefore, the inhibition of TLT formation may offer a novel therapeutic strategy for AKI in the elderly. PMID:27699223

  12. PrPCWD in rectal lymphoid tissue of deer (Odocoileus spp.).

    PubMed

    Wolfe, Lisa L; Spraker, Terry R; González, Lorenzo; Dagleish, Mark P; Sirochman, Tracey M; Brown, Jeremy C; Jeffrey, Martin; Miller, Michael W

    2007-07-01

    The utility of rectal lymphoid tissue sampling for the diagnosis of chronic wasting disease (CWD) infections in mule deer (Odocoileus hemionus) and white-tailed deer (Odocoileus virginianus) was evaluated. CWD-associated prion protein (PrP(CWD)) deposits were observed in the rectal mucosa from 19 orally inoculated mule deer by 381 days post-inoculation (p.i.); similarly, 45 out of 50 naturally infected mule deer had PrP(CWD) in their rectal mucosa. In orally inoculated white-tailed deer, the presence of glycine (G) or serine (S) at codon 96 of the native PrP (denoted 96GG, 96GS or 96SS) appeared to influence the temporal patterns of PrP(CWD) deposition: nine out of 11 infected 96GG individuals had PrP(CWD) in their rectal mucosa by 342 days p.i., whereas only three out of seven infected 96GS individuals had PrP(CWD) in their rectal mucosa by 381 days p.i. and none of three 96SS individuals had PrP(CWD) in their rectal mucosa by 751 days p.i. These findings support further evaluation of rectal mucosa sampling in CWD surveillance.

  13. Nucleases in immunity. I. The effect of immunization on RNase and DNase activity in lymphoid tissues

    PubMed Central

    Chakrabarty, A. K.; Friedman, H.

    1970-01-01

    The level of RNase and DNase in the spleen, lymph nodes and thymus glands of mice immunized with sheep erythrocytes was determined. Within 12 hr after immunization there was a moderate decrease in the level of specific RNase activity in the spleen. The depression persisted for several days and then returned to normal. The level of DNase activity also decreased in the spleen of immunized animals, returning to near normal levels on day 4 to 5 and increasing moderately by day 6 and 8. RNase activity in the lymph nodes and thymus increased rapidly after immunization, reaching a peak level several fold higher than in control animals on days 2 and 6. The level of DNase activity in lymph nodes and thymus was also elevated during the first few days after immunization, but to a lesser extent. The changes in total enzyme activity generally preceded the appearance of haemolytic plaque forming cells. Most of the antibody forming cells were present in the spleen, with peak numbers at day 4. Much fewer antibody forming cells were present in the lymph nodes, and even fewer in the thymus. The relationship between immunogenesis and nucleic acid metabolism in lymphoid tissue was discussed. PMID:4920599

  14. Development, Alteration and Real Time Dynamics of Conjunctiva-Associated Lymphoid Tissue

    PubMed Central

    Hüttmann, Gereon; Koop, Norbert; Bölke, Torsten; Gebert, Andreas; Stern, Michael E.; Niederkorn, Jerry Y.; Steven, Philipp

    2013-01-01

    Purpose Conjunctiva-associated lymphoid tissue (CALT) is thought to play a key role in initiating ocular surface related immune responses. This study was planned to get first profound insights into the function of CALT related to development, cellular dynamics and morphological alteration using a novel mouse model. Methods Expression and morphology of CALT were investigated using BALB/c mice kept under different housing conditions, after topical antigen-stimulation and following lymphadenectomy and splenectomy. Particles and bacteria were applied topically to study antigen-transport. Intravital visualization was performed using two-photon microscopy. Results Postnatal development and ultrastructure of CALT in the mouse is similar to humans. Topical antigen-challenge significantly alters CALT expression. Bacterial translocation is demonstrated via lymphoepithelium whereas cellular velocities within follicles were approximately 8 µm/min. Conclusions CALT in the mouse is an immunological interface of the ocular surface, featuring dynamic processes such as morphological plasticity, particle/bacteria transport and cellular migration. PMID:24376530

  15. Immune suppression of human lymphoid tissues and cells in rotating suspension culture and onboard the International Space Station

    PubMed Central

    Fitzgerald, Wendy; Chen, Silvia; Walz, Carl; Zimmerberg, Joshua; Margolis, Leonid

    2013-01-01

    The immune responses of human lymphoid tissue explants or cells isolated from this tissue were studied quantitatively under normal gravity and microgravity. Microgravity was either modeled by solid body suspension in a rotating, oxygenated culture vessel or was actually achieved on the International Space Station (ISS). Our experiments demonstrate that tissues or cells challenged by recall antigen or by polyclonal activator in modeled microgravity lose all their ability to produce antibodies and cytokines and to increase their metabolic activity. In contrast, if the cells were challenged before being exposed to modeled microgravity suspension culture, they maintained their responses. Similarly, in microgravity in the ISS, lymphoid cells did not respond to antigenic or polyclonal challenge, whereas cells challenged prior to the space flight maintained their antibody and cytokine responses in space. Thus, immune activation of cells of lymphoid tissue is severely blunted both in modeled and true microgravity. This suggests that suspension culture via solid body rotation is sufficient to induce the changes in cellular physiology seen in true microgravity. This phenomenon may reflect immune dysfunction observed in astronauts during space flights. If so, the ex vivo system described above can be used to understand cellular and molecular mechanisms of this dysfunction. PMID:19609626

  16. Immune suppression of human lymphoid tissues and cells in rotating suspension culture and onboard the International Space Station.

    PubMed

    Fitzgerald, Wendy; Chen, Silvia; Walz, Carl; Zimmerberg, Joshua; Margolis, Leonid; Grivel, Jean-Charles

    2009-12-01

    The immune responses of human lymphoid tissue explants or cells isolated from this tissue were studied quantitatively under normal gravity and microgravity. Microgravity was either modeled by solid body suspension in a rotating, oxygenated culture vessel or was actually achieved on the International Space Station (ISS). Our experiments demonstrate that tissues or cells challenged by recall antigen or by polyclonal activator in modeled microgravity lose all their ability to produce antibodies and cytokines and to increase their metabolic activity. In contrast, if the cells were challenged before being exposed to modeled microgravity suspension culture, they maintained their responses. Similarly, in microgravity in the ISS, lymphoid cells did not respond to antigenic or polyclonal challenge, whereas cells challenged prior to the space flight maintained their antibody and cytokine responses in space. Thus, immune activation of cells of lymphoid tissue is severely blunted both in modeled and true microgravity. This suggests that suspension culture via solid body rotation is sufficient to induce the changes in cellular physiology seen in true microgravity. This phenomenon may reflect immune dysfunction observed in astronauts during space flights. If so, the ex vivo system described above can be used to understand cellular and molecular mechanisms of this dysfunction.

  17. Morphologic observation of mucosa-associated lymphoid tissue in the large intestine of Bactrian camels (Camelus bactrianus).

    PubMed

    ZhaXi, Yingpai; Wang, Wenhui; Zhang, Wangdong; Gao, Qiang; Guo, Minggang; Jia, Shuai

    2014-07-01

    The structure and distribution of the mucosa-associated lymphoid tissue (MALT) throughout the large intestine of 10 Bactrian camels were comparatively studied by anatomical and histological methods. The results showed that Peyer's patches (PPs) were mainly located on the mucosal surfaces of the entire ileocecal orifice, the beginning of the cecum and the first third of the colon. The shape of PPs gradually changed from "scrotiform" to "faviform" along the large intestine with the scrotiform PP as the major type in the ileocecal orifice. The distribution density also gradually decreased from the ileocecal orifice to the colon. The histological observations further revealed that the MALT in the form of PPs or isolated lymphoid follicles (ILF) and lamina propria lymphocytes was mainly present in the lamina propria and submucosa from the entire ileocecal orifice, where the muscularis mucosa is usually incomplete, to the colonic forepart. In addition, lymphoid tissue was much more abundant in the lamina propria and submucosa of the ileocecal orifice as compared to the cecum and colon. Statistically, the MALT of the ileocecal orifice contained a higher number of lymphoid follicles (37.7/10 mm(2) ) than that of the cecum, colon, or rectum (P < 0.05). The germinal centers of the lymphoid follicles were clearly visible. Together, our data suggest that the ileocecal orifice constitutes the main inductive site for the mucosal immunity in the large intestine of the Bactrian camel; and that scrotiform PPs are likely to the result of long-term adaptation of the Bactrian camel to the harsh living environment. © 2014 Wiley Periodicals, Inc.

  18. Targeted delivery of antigen to hamster nasal lymphoid tissue with M-cell-directed lectins.

    PubMed Central

    Giannasca, P J; Boden, J A; Monath, T P

    1997-01-01

    The nasal cavity of a rodent is lined by an epithelium organized into distinct regional domains responsible for specific physiological functions. Aggregates of nasal lymphoid tissue (NALT) located at the base of the nasal cavity are believed to be sites of induction of mucosal immune responses to airborne antigens. The epithelium overlying NALT contains M cells which are specialized for the transcytosis of immunogens, as demonstrated in other mucosal tissues. We hypothesized that NALT M cells are characterized by distinct glycoconjugate receptors which influence antigen uptake and immune responses to transcytosed antigens. To identify glycoconjugates that may distinguish NALT M cells from other cells of the respiratory epithelium (RE), we performed lectin histochemistry on sections of the hamster nasal cavity with a panel of lectins. Many classes of glycoconjugates were found on epithelial cells in this region. While most lectins bound to sites on both the RE and M cells, probes capable of recognizing alpha-linked galactose were found to label the follicle-associated epithelium (FAE) almost exclusively. By morphological criteria, the FAE contains >90% M cells. To determine if apical glycoconjugates on M cells were accessible from the nasal cavity, an M-cell-selective lectin and a control lectin in parallel were administered intranasally to hamsters. The M-cell-selective lectin was found to specifically target the FAE, while the control lectin did not. Lectin bound to M cells in vivo was efficiently endocytosed, consistent with the role of M cells in antigen transport. Intranasal immunization with lectin-test antigen conjugates without adjuvant stimulated induction of specific serum immunoglobulin G, whereas antigen alone or admixed with lectin did not. The selective recognition of NALT M cells by a lectin in vivo provides a model for microbial adhesin-host cell receptor interactions on M cells and the targeted delivery of immunogens to NALT following intranasal

  19. [Successful rituximab monotherapy in a patient with mucosa-associated lymphoid tissue lymphoma of the rectum with trisomy 3, 18].

    PubMed

    Kagawa, Miwako; Okamura, Seisuke; Okamoto, Koichi; Kitamura, Shinji; Kimura, Tetsuo; Niki, Miyako; Kaji, Masako; Okahisa, Toshiya; Yano, Mitsuyasu; Kagawa, Seiko; Kudo, Eiji; Sano, Toshiaki; Imoto, Yoshitaka; Wada, Satoshi; Takayama, Tetsuji

    2010-04-01

    A 62-year-old man was referred to our hospital with enlargement of mucosa-associated lymphoid tissue (MALT) lymphoma of the rectum after the eradication of Helicobacter pylori. The patient was given a diagnosis of stage I MALT. Endoscopic observation revealed an enlarged rectal tumor with 3, 18 double trisomy. Rituximab monotherapy was given and complete remission was achieved. Rituximab monotherapy can be useful for MALT lymphoma of the rectum.

  20. Detection of bcl-2 rearrangement in mucosa-associated lymphoid tissue lymphomas from patients with hepatitis C virus infection.

    PubMed

    Libra, Massimo; De Re, Valli; Gloghini, Annunziata; Gasparotto, Daniela; Gragnani, Laura; Navolanic, Patrick M; De Vita, Salvatore; Mazzarino, Maria Clorinda; Zignego, Anna Linda; Carbone, Antonino; Boiocchi, Mauro

    2004-07-01

    It has been shown that t(14;18)(q32;q21) involving fusion of IGH with MALT1 occurs frequently in mucosa-associated lymphoid tissue (MALT) lymphomas. Results of the present study indicate that the classical form of t(14;18)(q32;q21) involving fusion of IGH with bcl-2 can be detectable in a subset of MALT lymphomas in patients with hepatitis C virus (HCV) infection.

  1. Helicobacter pylori-negative gastric mucosa-associated lymphoid tissue lymphomas: A review.

    PubMed

    Asano, Naoki; Iijima, Katsunori; Koike, Tomoyuki; Imatani, Akira; Shimosegawa, Tooru

    2015-07-14

    Since Isaacson and Wright first reported on the extra-nodal marginal zone B-cell lymphoma of the stomach in 1983, following studies have clarified many aspects of this disease. We now know that the stomach is the most affected organ by this disease, and approximately 90% of gastric mucosa-associated lymphoid tissue (MALT) lymphomas are related to Helicobacter pylori (H. pylori) infection. This implies that approximately 10% of gastric MALT lymphomas occur independent of H. pylori infection. The pathogenesis of these H. pylori-negative gastric MALT lymphomas remains unclear. To date, there have been several speculations. One possibility is that genetic alterations result in nuclear factor-kappa B (NF-κB) activation. Among these alterations, t(11;18)(q21;q21) is more frequently observed in H. pylori-negative gastric MALT lymphomas, and such translocation results in the synthesis of fusion protein API2-MALT1, which causes canonical and noncanonical NF-κB activation. Another possibility is infection with bacteria other than H. pylori. This could explain why H. pylori eradication therapy can cure some proportions of H. pylori-negative gastric MALT lymphoma patients, although the bacteria responsible for MALT lymphomagenesis are yet to be defined. Recent advances in endoscopy suggest magnifying endoscopy with narrow band imaging as a useful tool for both detecting gastric MALT lymphoma lesions and judging the response to treatment. A certain proportion of H. pylori-negative gastric MALT lymphoma patients respond to eradication therapy; hence, H. pylori eradication therapy could be considered as a first-line treatment for gastric MALT lymphomas regardless of their H. pylori infection status.

  2. Prebiotics modulate immune responses in the gut-associated lymphoid tissue of chickens.

    PubMed

    Janardhana, Vijaya; Broadway, Mary M; Bruce, Matthew P; Lowenthal, John W; Geier, Mark S; Hughes, Robert J; Bean, Andrew G D

    2009-07-01

    The recent European Union ban on the prophylactic use of in-feed antibiotics has escalated the search for alternatives for use within the poultry industry. When evaluating the efficacy of potential antibiotic alternatives on bird health and productivity, it is important to analyze the competence of the immune cells in the gut-associated lymphoid tissue (GALT), because it is routinely involved in the surveillance of colonizing microbes as well as in interacting with the ingested feed antigens. Therefore, we studied the effect of the prebiotics mannan-oligosaccharide (MOS) and fructo-oligosaccharide (FOS) on the phenotypic and functional competence of immune cells in cecal tonsil (CT), which is a major GALT. Day-old Cobb 500 male broilers were randomized to 4 groups. Control chickens were fed the basal diet only. Chickens in experimental groups received 0.05 g/kg zinc bacitracin or 5 g/kg of either FOS or MOS in addition to basal diet. At the end of 25 d, our comparison of the experimental groups with controls revealed that the addition of prebiotics to diet resulted in a significant reduction in the proportion of B cells and in mitogen responsiveness of lymphocytes in CT. Furthermore, FOS treatment significantly enhanced the IgM and IgG antibody titers in plasma. These findings emphasize the need for the analyses of the gut immune function following treatment with novel feed additives. The knowledge obtained from such analyses may aid in understanding the mechanisms underlying the immune competence of the birds, which needs consideration when selecting and optimizing new feed additives instead of antibiotics for poultry production.

  3. Treatment Effects and Sequelae of Radiation Therapy for Orbital Mucosa-Associated Lymphoid Tissue Lymphoma

    SciTech Connect

    Hata, Masaharu; Omura, Motoko; Koike, Izumi; Tomita, Naoto; Iijima, Yasuhito; Tayama, Yoshibumi; Odagiri, Kazumasa; Minagawa, Yumiko; Ogino, Ichiro; Inoue, Tomio

    2011-12-01

    Purpose: Among extranodal lymphomas, orbital mucosa-associated lymphoid tissue (MALT) lymphoma is a relatively rare presentation. We performed a review to ascertain treatment efficacy and toxicity of radiation therapy for orbital MALT lymphoma. We also evaluated changes in visual acuity after irradiation. Methods and Materials: Thirty patients with orbital MALT lymphoma underwent radiation therapy with curative intent. Clinical stages at diagnosis were stage I{sub E}A in 29 patients and stage II{sub E}A in 1 patient. Total doses of 28.8 to 45.8 Gy (median, 30 Gy) in 15 to 26 fractions (median, 16 fractions) were delivered to the tumors. Results: All irradiated tumors were controlled during the follow-up period of 2 to 157 months (median, 35 months) after treatment. Two patients had relapses that arose in the cervical lymph node and the ipsilateral palpebral conjunctiva outside the radiation field at 15 and 67 months after treatment, respectively. The 5-year local progression-free and relapse-free rates were 100% and 96%, respectively. All 30 patients are presently alive; the overall and relapse-free survival rates at 5 years were 100% and 96%, respectively. Although 5 patients developed cataracts of grade 2 at 8 to 45 months after irradiation, they underwent intraocular lens implantation, and their eyesight recovered. Additionally, there was no marked deterioration in the visual acuity of patients due to irradiation, with the exception of cataracts. No therapy-related toxicity of grade 3 or greater was observed. Conclusions: Radiation therapy was effective and safe for patients with orbital MALT lymphoma. Although some patients developed cataracts after irradiation, visual acuity was well preserved.

  4. Pulmonary mucosa-associated lymphoid tissue lymphoma associated with pulmonary sarcoidosis: a case report and literature review.

    PubMed

    Kokuho, Nariaki; Terasaki, Yasuhiro; Urushiyama, Hirokazu; Terasaki, Mika; Kunugi, Shinobu; Morimoto, Taisuke; Azuma, Arata; Usuda, Jitsuo; Gemma, Akihiko; Eishi, Yoshinobu; Shimizu, Akira

    2016-05-01

    Differentiating low-grade lymphoma from preexisting sarcoidosis is difficult because of their pathological similarity. This article describes a case of pulmonary mucosa-associated lymphoid tissue lymphoma associated with pulmonary sarcoidosis. The patient, a 45-year-old Japanese man, presented with a 10-year history of pulmonary sarcoidosis and 5-year history of ocular sarcoidosis with histologic findings. Because only the right S3 lung nodule had gradually enlarged, partial resection was performed. Pathological study revealed noncaseous epithelioid granulomas with lymphoplasmacytic proliferation but also marked lymphoid cell proliferation with lymphoepithelial lesion findings that differed from findings of typical sarcoid lesions. Our lymphoepithelial lesion evaluation via immunohistochemistry and analysis of Ig heavy-chain gene rearrangements with assessment of Propionibacterium acnes-specific antibody reactions allow us to report, for the first time, this case of pulmonary mucosa-associated lymphoid tissue lymphoma associated with pulmonary sarcoidosis in exactly the same location, which may be significant for differentiating these diseases and understanding their pathogenic association.

  5. Decreased human immunodeficiency virus type 1 plasma viremia during antiretroviral therapy reflects downregulation of viral replication in lymphoid tissue.

    PubMed Central

    Cohen, O J; Pantaleo, G; Holodniy, M; Schnittman, S; Niu, M; Graziosi, C; Pavlakis, G N; Lalezari, J; Bartlett, J A; Steigbigel, R T

    1995-01-01

    Although several immunologic and virologic markers measured in peripheral blood are useful for predicting accelerated progression of human immunodeficiency virus (HIV) disease, their validity for evaluating the response to antiretroviral therapy and their ability to accurately reflect changes in lymphoid organs remain unclear. In the present study, changes in certain virologic markers have been analyzed in peripheral blood and lymphoid tissue during antiretroviral therapy. Sixteen HIV-infected individuals who were receiving antiretroviral therapy with zidovudine for > or = 6 months were randomly assigned either to continue on zidovudine alone or to add didanosine for 8 weeks. Lymph node biopsies were performed at baseline and after 8 weeks. Viral burden (i.e., HIV DNA copies per 10(6) mononuclear cells) and virus replication in mononuclear cells isolated from peripheral blood and lymph node and plasma viremia were determined by semiquantitative polymerase chain reaction assays. Virologic and immunologic markers remained unchanged in peripheral blood and lymph node of patients who continued on zidovudine alone. In contrast, a decrease in virus replication in lymph nodes was observed in four of six patients who added didanosine to their regimen, and this was associated with a decrease in plasma viremia. These results indicate that decreases in plasma viremia detected during antiretroviral therapy reflect downregulation of virus replication in lymphoid tissue. Images Fig. 1 Fig. 2 Fig. 3 PMID:7597072

  6. Immunohistochemical investigation of cells expressing CD21, membrane IgM, CD32 and a follicular dendritic cell marker in the lymphoid tissues of neonatal calves.

    PubMed

    Chattha, Kuldeep S; Hodgins, Douglas C; DeLay, Josepha; Antoine, Nadine; Shewen, Patricia E

    2010-10-15

    Activation of B lymphocytes in the presence of passive maternal antibodies depends on expression of CD21, membrane IgM and CD32. On colligation with IgM, CD32 inhibits activation whereas CD21 enhances it. Recently, we assessed expression of CD21 and CD32 on IgM(+) cells from lymphoid tissues of newborn calves by flow cytometry, but this approach does not provide information about spatial distribution within lymphoid compartments. Therefore, histologic sections of lymphoid tissues from newborn and 7-month-old calves were examined using an immunoperoxidase technique. In all calves, CD21 and IgM stained cells were collocated in the cortex and paracortex of the retropharyngeal lymph node, in the marginal zone of the spleen and in lymphoid aggregates of palatine tonsils. Most CD32(+) cells were in the mantle zone of lymphoid follicles in 7-month-old calves, whereas only weak staining was observed in newborns. A few CD32(+) cells were also observed in the paracortex at both ages. Absence of CD32(+) cells in the center of follicles suggests that IgM(+)CD32(-) cells observed previously by flow cytometry were from germinal centers. Overall, there were few organized lymphoid aggregates within lymphoid tissues of newborn calves, and follicular dendritic cells were virtually undetectable. Their absence may be an important limitation for neonatal immunization.

  7. Malignant catarrhal fever induced by Alcelaphine herpesvirus 1 is characterized by an expansion of activated CD3+CD8+CD4- T cells expressing a cytotoxic phenotype in both lymphoid and non-lymphoid tissues.

    PubMed

    Dewals, Benjamin G; Vanderplasschen, Alain

    2011-08-22

    Alcelaphine herpesvirus 1 (AlHV-1) is carried by wildebeest asymptomatically. It causes a fatal lymphoproliferative disease named wildebeest-derived malignant catarrhal fever (WD-MCF) when cross-species transmitted to a variety of susceptible species of the Artiodactyla order. WD-MCF can be reproduced experimentally in rabbits. In a previous report, we demonstrated that WD-MCF induced by AlHV-1 is associated with a severe proliferation of CD8(+) T cells in the lymphoid tissues. Here, we further studied the mononuclear leukocytic populations in both the lymphoid (throughout the infection and at time of euthanasia) and non-lymphoid (at time of euthanasia) organs during WD-MCF induced experimentally in rabbits. To reach that goal, we performed multi-colour flow cytometry stainings. The results obtained demonstrate that the development of WD-MCF correlates in peripheral blood with a severe increase of CD8(+) cell percentages; and that CD3(+)CD8(+)CD4(-) T cells were the predominant cell type in both lymphoid and non-lymphoid organs at time of euthanasia. Further characterization of the mononuclear leukocytes isolated from both lymphoid and non-lymphoid tissues revealed that the CD8(+) T cells express high levels of the activation markers CD25 and CD44, produce high amount of gamma-interferon (IFN-γ) and perforin, and showed a reduction of interleukin-2 (IL-2) gene expression. These data demonstrate that the development of WD-MCF is associated with the expansion and infiltration of activated and cytotoxic CD3(+)CD8(+)CD4(-) T cells secreting high amount of IFN-γ but low IL-2.

  8. Absence of tissue factor is characteristic of lymphoid malignancies of both T- and B-cell origin

    PubMed Central

    Cesarman-Maus, Gabriela; Braggio, Esteban; Lome-Maldonado, Carmen; Morales-Leyte, Ana Lilia; Fonseca, Rafael

    2014-01-01

    Summary Background Thrombosis is a marker of poor prognosis in individuals with solid tumors. The expression of tissue factor (TF) on the cell surface membrane of malignant cells is a pivotal molecular link between activation of coagulation, angiogenesis, metastasis, aggressive tumor behavior and poor survival. Interestingly, thrombosis is associated with shortened survival in solid, but not in lymphoid neoplasias. Objectives We sought to study whether the lack of impact of thrombosis on survival in lymphoid neoplasias could be due to a lack of tumor-derived TF expression. Methods We analyzed TF gene (F3) expression in lymphoid (N=114), myeloid (N=49) and solid tumor (N=856) cell lines using the publicly available dataset from the Broad-Novartis Cancer Cell Line Encyclopedia (http://www.broadinstitute.org/ccle/home), and in 90 patient-derived lymphoma samples. TF protein expression was studied by immunohistochemistry (IHC). Results In sharp contrast to wide F3 expression in solid tumors (74.2%), F3 was absent in all low and high grade T- and B-cell lymphomas, and in most myeloid tumors, except for select acute myeloid leukemias with monocytic component. IHC confirmed the absence of TF protein in all indolent and high-grade B-cell (0/90) and T-cell (0/20) lymphomas, and acute leukemias (0/11). Conclusions We show that TF in lymphomas does not derive from the malignant cells, since these do not express either F3 or TF protein. Therefore, it is unlikely that thrombosis in patients with lymphoid neoplasms is secondary to tumor-derived tissue factor. PMID:24491425

  9. [Cytoarchitecture of lymphoid tissue in tracheal mucosa as affected by diamond dust].

    PubMed

    Garmaeva, D K

    2005-01-01

    The effect of diamond dust on lymphoid aggregates in tracheal mucosa after the exposure for various time periods was studied in mature Wistar rats, which were placed under the natural conditions of diamond-processing factory. Exposure to diamond dust resulted in the changes of cell content of lymphoid aggregates in tracheal mucosa already at the early stages of an experiment (Day 3). The proportion of small lymphocytes was decreased, while the content of medium lymphocytes and undifferentiated cells was increased simultaneously with the augmentation of the number of macrophages and cells undergoing destruction. At Day 30 in subepithelial area and in the basal region of lymphoid nodules, the reduction of the number of small lymphocytes was also accompanied by the significant increase of macrophages and cells undergoing destruction.

  10. PrP(Sc) deposition in nervous tissues without lymphoid tissue involvement is frequently found in ARQ/ARQ Sarda breed sheep preclinically affected with natural scrapie.

    PubMed

    Ligios, C; Cancedda, M G; Madau, L; Santucciu, C; Maestrale, C; Agrimi, U; Ru, G; Di Guardo, G

    2006-10-01

    The pathogenesis of natural scrapie in Sarda breed sheep was investigated in 1050 asymptomatic and 49 sick sheep from scrapie-affected flocks. Central and peripheral nervous system, along with lymphoreticular system (LRS) tissues, were subjected to immunohistochemistry (IHC) and Western-blotting (WB) for detection of pathological isoform of the prion protein (PrP(Sc)). A total of 69 of the 1050 clinically healthy sheep were found to be infected with scrapie, with PrP(Sc) being detected in both the central nervous system (CNS) and enteric nervous system (ENS) plexuses of 60 of the sheep, while IHC and WB yielded evidence of (PrP(Sc)) deposition only in lymphoid tissues of the remaining 9 clinically healthy sheep. PrP(Sc) was also detected in the CNS, as well as in ENS plexuses from all of the 49 clinically affected sheep. Nevertheless, 18 of the 69 clinically healthy animals (26%, 17 ARQ/ARQ and 1 ARQ/AHQ sheep), along with 3 ARQ/ARQ sheep (6%) of the clinically affected group, showed no IHC or WB evidence of PrP(Sc) in lymphoid tissues, but PrP(Sc) could be still detected in their CNS and ENS plexuses. The study demonstrates dual CNS and ENS PrP(Sc) deposition in Sarda sheep with scrapie, in spite of an apparent lack of lymphoid tissue involvement in a number of cases.

  11. Nerve growth factor and cytokines mediate lymphoid tissue-induced neurite outgrowth from mouse superior cervical ganglia in vitro.

    PubMed

    Kannan, Y; Bienenstock, J; Ohta, M; Stanisz, A M; Stead, R H

    1996-07-01

    Superior cervical ganglia (SCG) from neonatal mice were cultured with adult murine lymphoid tissue explants in Matrigel (Collaborative Biomedical, Bedford, MA). After 1 and 2 days in culture, many neurites grew toward thymus and spleen. Normal mesenteric lymph node (MLN) induced a smaller effect; however, activated MLN (isolated from mice 10 days after infection with Nippostrongylus brasiliensis; Nb-MLN-10d) caused significantly increased neurite outgrowth. To determine the roles of nerve growth factor (NGF) and cytokines in the promotion of neuritogenesis by lymphoid tissues, anti-NGF and various anti-cytokines were added to cocultures. Anti-NGF inhibited most of the neurite outgrowth toward thymus and spleen but only partially that toward Nb-MLN-10d. Anti-mouse IL-1 beta also significantly reduced the number of neurites growing toward thymus, spleen, and normal MLN. The number of neurites growing toward Nb-MLN-10d was significantly reduced by anti-IL-1 beta, anti-IL-3, anti-IL-6, or anti-GM-CSF. Exogenous IL-1 beta and IL-3 caused neurite outgrowth in single SCG cultures; and the IL-1 beta-, but not the IL-3-, mediated effect was completely blocked by anti-NGF. In one-day thymus/SCG cocultures, endogenous IL-1 was not detectable at concentrations sufficient to cause nerve growth; however, ample NGF was present in the thymic tissues and culture supernatants, but not in SCG. These data suggest that IL-1 mediates NGF production in lymphoid tissues, which in turn induces the growth of sympathetic nerves. Moreover, IL-3, IL-6, or GM-CSF produced during inflammation might also play important roles in the stimulation of nerve growth in vivo.

  12. Genomic Modifiers of Natural Killer Cells, Immune Responsiveness and Lymphoid Tissue Remodeling Together Increase Host Resistance to Viral Infection

    PubMed Central

    Lee, Heather; Prince, Jessica; Stadnisky, Michael D.; Anderson, Monique; Nash, William; Rival, Claudia; Wei, Hairong; Gamache, Awndre; Farber, Charles R.; Tung, Kenneth; Brown, Michael G.

    2016-01-01

    The MHC class I Dk molecule supplies vital host resistance during murine cytomegalovirus (MCMV) infection. Natural killer (NK) cells expressing the Ly49G2 inhibitory receptor, which specifically binds Dk, are required to control viral spread. The extent of Dk-dependent host resistance, however, differs significantly amongst related strains of mice, C57L and MA/My. As a result, we predicted that relatively small-effect modifier genetic loci might together shape immune cell features, NK cell reactivity, and the host immune response to MCMV. A robust Dk-dependent genetic effect, however, has so far hindered attempts to identify additional host resistance factors. Thus, we applied genomic mapping strategies and multicolor flow cytometric analysis of immune cells in naive and virus-infected hosts to identify genetic modifiers of the host immune response to MCMV. We discovered and validated many quantitative trait loci (QTL); these were mapped to at least 19 positions on 16 chromosomes. Intriguingly, one newly discovered non-MHC locus (Cmv5) controlled splenic NK cell accrual, secondary lymphoid organ structure, and lymphoid follicle development during MCMV infection. We infer that Cmv5 aids host resistance to MCMV infection by expanding NK cells needed to preserve and protect essential tissue structural elements, to enhance lymphoid remodeling and to increase viral clearance in spleen. PMID:26845690

  13. An unusual presentation of gastric mucosa-associated lymphoid tissue (MALT)-type lymphoma

    PubMed Central

    Shrestha, Bikram; Kim, Bernard; Huffstetler, Alison

    2016-01-01

    Mucosa-associated lymphoid tissue (MALT)-type lymphoma is a relatively rare disease; nevertheless, it is the third most common lymphoma type, accounting for 5–7% of all non-Hodgkin lymphomas. Case series and retrospective analysis published in the literature have suggested that extra gastrointestinal (GI) MALT-type lymphoma can occur simultaneously with MALT-type lymphoma involving the GI tract. We report the case of a healthy, 64-year-old Caucasian male who presented with progressive fatigue, non-productive cough, and worsening exertional shortness of breath for 3 months who was subsequently diagnosed with gastric extra-nodal marginal zone B-cell lymphoma or MALToma with simultaneous metastasis to the lung (bronchi) based on biopsy reports. Case presentation A 64-year-old Caucasian male presented to the emergency room complaining of progressive fatigue for 3 months which had progressed to the point of hindering his usual activities of daily living (ADL). He had recently visited his primary care provider for evaluation of a non-productive cough and exertional shortness of breath. A chest radiography obtained at the time showed bilateral infiltrates. He was then treated for atypical pneumonia but his symptoms unfortunately did not improve. Initial investigations in the emergency room revealed severe anemia and a positive stool guaiac test. Imaging showed bilateral pulmonary infiltrates and an irregular gastric mass. Gastric and transbronchial biopsies were suggestive of extra-nodal marginal zone B-cell lymphoma with simultaneous metastasis to the bronchi. He was treated symptomatically with transfusion of packed red blood cells (PRBC) and intravenous iron followed by radiotherapy. Helicobacter pylori infection was ruled out eliminating the possibility of treating him with eradication therapy. Conclusion Although the stomach is the most common and most extensively studied site of involvement of MALT lymphomas, they can also emerge in many other locations. MALT

  14. Synchronous primary adenocarcinoma, mucosa-associated lymphoid tissue lymphoma and a stromal tumor in a Helicobacter pylori-infected stomach.

    PubMed

    Kaffes, Arthur; Hughes, Louise; Hollinshead, John; Katelaris, Peter

    2002-09-01

    We report the case of a 78-year-old man with Helicobacter pylori infection and three primary neoplasms of the stomach: adenocarcinoma, mucosa-associated lymphoid tissue (MALT) lymphoma and a gastrointestinal stromal cell tumor. Helicobacter pylori infection is associated with gastric carcinoma and MALT lymphoma, although their simultaneous occurrence is rare. Gastrointestinal stromal cell tumors have not been associated with infection to date. This appears to be the first report of the synchronous occurrence of these three gastric tumors. Copyright 2002 Blackwell Publishing Asia Pty Ltd

  15. [Specific clinical and immunological features of chronic diseases of the nasal-associated lymphoid tissue in the children].

    PubMed

    Beniova, S N; Taranova, S V; Babko, S V

    2014-01-01

    The objective of the present work was to study the structure, clinical, and immunological features of various etiological variants of chronic diseases of the nasal-associated lymphoid tissue in the children. A total of 142 children at the age from 3 to 7 years presenting with this pathological condition were available for the observation. The study revealed differences in the clinical course of the disease and the cytokine response (IL-6, Ril-6, TNF, sYNFR55, sTNFR75) at the local and systemic levels for different pathogens (S. aureus, S. pneumoniae, S. pyrogenes).

  16. The chemokine receptor CXCR5 is pivotal for ectopic mucosa-associated lymphoid tissue neogenesis in chronic Helicobacter pylori-induced inflammation.

    PubMed

    Winter, Susann; Loddenkemper, Christoph; Aebischer, Anton; Räbel, Katrin; Hoffmann, Kirstin; Meyer, Thomas F; Lipp, Martin; Höpken, Uta E

    2010-11-01

    Ectopic lymphoid follicles are a key feature of chronic inflammatory autoimmune and infectious diseases, such as rheumatoid arthritis, Sjögren's syndrome, and Helicobacter pylori-induced gastritis. Homeostatic chemokines are considered to be involved in the formation of such tertiary lymphoid tissue. High expression of CXCL13 and its receptor, CXCR5, has been associated with the formation of ectopic lymphoid follicles in chronic infectious diseases. Here, we defined the role of CXCR5 in the development of mucosal tertiary lymphoid tissue and gastric inflammation in a mouse model of chronic H. pylori infection. CXCR5-deficient mice failed to develop organized gastric lymphoid follicles despite similar bacterial colonization density as infected wild-type mice. CXCR5 deficiency altered Th17 responses but not Th1-type cellular immune responses to H. pylori infection. Furthermore, CXCR5-deficient mice exhibited lower H. pylori-specific serum IgG and IgA levels and an overall decrease in chronic gastric immune responses. In conclusion, the development of mucosal tertiary ectopic follicles during chronic H. pylori infection is strongly dependent on the CXCL13/CXCR5 signaling axis, and lack of de novo lymphoid tissue formation attenuates chronic immune responses.

  17. Macrophage entry mediated by HIV Envs from brain and lymphoid tissues is determined by the capacity to use low CD4 levels and overall efficiency of fusion

    SciTech Connect

    Thomas, Elaine R.; Dunfee, Rebecca L.; Stanton, Jennifer; Bogdan, Derek; Taylor, Joann; Kunstman, Kevin; Bell, Jeanne E.; Wolinsky, Steven M.; Gabuzda, Dana . E-mail: dana_gabuzda@dfci.harvard.edu

    2007-03-30

    HIV infects macrophages and microglia in the central nervous system (CNS), which express lower levels of CD4 than CD4+ T cells in peripheral blood. To investigate mechanisms of HIV neurotropism, full-length env genes were cloned from autopsy brain and lymphoid tissues from 4 AIDS patients with HIV-associated dementia (HAD). Characterization of 55 functional Env clones demonstrated that Envs with reduced dependence on CD4 for fusion and viral entry are more frequent in brain compared to lymphoid tissue. Envs that mediated efficient entry into macrophages were frequent in brain but were also present in lymphoid tissue. For most Envs, entry into macrophages correlated with overall fusion activity at all levels of CD4 and CCR5. gp160 nucleotide sequences were compartmentalized in brain versus lymphoid tissue within each patient. Proline at position 308 in the V3 loop of gp120 was associated with brain compartmentalization in 3 patients, but mutagenesis studies suggested that P308 alone does not contribute to reduced CD4 dependence or macrophage-tropism. These results suggest that HIV adaptation to replicate in the CNS selects for Envs with reduced CD4 dependence and increased fusion activity. Macrophage-tropic Envs are frequent in brain but are also present in lymphoid tissues of AIDS patients with HAD, and entry into macrophages in the CNS and other tissues is dependent on the ability to use low receptor levels and overall efficiency of fusion.

  18. Histology and immunohistochemistry of the gut-associated lymphoid tissue of the eastern grey kangaroo, Macropus giganteus.

    PubMed

    Old, J M; Deane, E M

    2001-12-01

    Mesenteric lymph nodes and gut-associated lymphoid tissue (GALT) from juvenile eastern grey kangaroos were investigated. The mesenteric nodes had a similar structure to that described for eutherian mammals. They contained distinct regions of medulla and cortex, with prominent follicles and germinal centres. Gut associated lymphoid tissue consisted of areas of submucosal follicles. These varied from areas of densely packed lymphocytes with darkly staining, prominent coronas to areas with no defined follicles. The distribution of T cells in these tissues was documented by use of species-crossreactive antibodies to the surface markers CD3 and CD5; B cells were identified by antibodies to CD79b. Within the lymph nodes T cells were located mainly in the paracortex and cortex, with limited numbers observed in the follicles; B cells were located on the marginal zone of the follicles. In GALT, T cells were located in the peripheral regions of the germinal centres of secondary follicles, while B cells were abundant in primary follicles. These observations are consistent with those made in a range of other marsupials (metatherian) and eutherian mammals and are indicative of the capacity to respond to antigens entering via the mouth.

  19. Lack of prion accumulation in lymphoid tissues of PRNP ARQ/ARR sheep intracranially inoculated with the agent of scrapie.

    PubMed

    Greenlee, Justin J; Kunkle, Robert A; Richt, Jürgen A; Nicholson, Eric M; Hamir, Amir N

    2014-01-01

    Sheep scrapie is a transmissible spongiform encephalopathy that can be transmitted horizontally. The prion protein gene (PRNP) profoundly influences the susceptibility of sheep to the scrapie agent and the tissue levels and distribution of PrPSc in affected sheep. The purpose of this study was to compare the survival time and PrPSc tissue distribution in sheep with highly resistant and highly susceptible PRNP genotypes after intracranial inoculation of the agent of scrapie. Five sheep each of genotype VRQ/VRQ, VRQ/ARR or ARQ/ARR were inoculated. Sheep were euthanized when clinical signs of scrapie became severe. Clinical signs, microscopic lesions, and western blot profiles were uniform across genotypes and consistent with manifestations of classical scrapie. Mean survival time differences were associated with the 171 polymorphic site with VRQ/VRQ sheep surviving 18 months, whereas VRQ/ARR and ARQ/ARR sheep survived 60 and 56 months, respectively. Labeling of PrPSc by immunohistochemistry revealed similar accumulations in central nervous system tissues regardless of host genotype. Immunoreactivity for PrPSc in lymphoid tissue was consistently abundant in VRQ/VRQ, present but confined to tonsil or retropharyngeal lymph node in 4/5 VRQ/ARR, and totally absent in ARQ/ARR sheep. The results of this study demonstrate the susceptibility of sheep with the ARQ/ARR genotype to scrapie by the intracranial inoculation route with PrPSc accumulation in CNS tissues, but prolonged incubation times and lack of PrPSc in lymphoid tissue.

  20. Lack of Prion Accumulation in Lymphoid Tissues of PRNP ARQ/ARR Sheep Intracranially Inoculated with the Agent of Scrapie

    PubMed Central

    Greenlee, Justin J.; Kunkle, Robert A.; Richt, Jürgen A.; Nicholson, Eric M.

    2014-01-01

    Sheep scrapie is a transmissible spongiform encephalopathy that can be transmitted horizontally. The prion protein gene (PRNP) profoundly influences the susceptibility of sheep to the scrapie agent and the tissue levels and distribution of PrPSc in affected sheep. The purpose of this study was to compare the survival time and PrPSc tissue distribution in sheep with highly resistant and highly susceptible PRNP genotypes after intracranial inoculation of the agent of scrapie. Five sheep each of genotype VRQ/VRQ, VRQ/ARR or ARQ/ARR were inoculated. Sheep were euthanized when clinical signs of scrapie became severe. Clinical signs, microscopic lesions, and western blot profiles were uniform across genotypes and consistent with manifestations of classical scrapie. Mean survival time differences were associated with the 171 polymorphic site with VRQ/VRQ sheep surviving 18 months, whereas VRQ/ARR and ARQ/ARR sheep survived 60 and 56 months, respectively. Labeling of PrPSc by immunohistochemistry revealed similar accumulations in central nervous system tissues regardless of host genotype. Immunoreactivity for PrPSc in lymphoid tissue was consistently abundant in VRQ/VRQ, present but confined to tonsil or retropharyngeal lymph node in 4/5 VRQ/ARR, and totally absent in ARQ/ARR sheep. The results of this study demonstrate the susceptibility of sheep with the ARQ/ARR genotype to scrapie by the intracranial inoculation route with PrPSc accumulation in CNS tissues, but prolonged incubation times and lack of PrPSc in lymphoid tissue. PMID:25233232

  1. Critical role of CD4 T cells in maintaining lymphoid tissue structure for immune cell homeostasis and reconstitution.

    PubMed

    Zeng, Ming; Paiardini, Mirko; Engram, Jessica C; Beilman, Greg J; Chipman, Jeffrey G; Schacker, Timothy W; Silvestri, Guido; Haase, Ashley T

    2012-08-30

    Loss of the fibroblastic reticular cell (FRC) network in lymphoid tissues during HIV-1 infection has been shown to impair the survival of naive T cells and limit immune reconstitution after antiretroviral therapy. What causes this FRC loss is unknown. Because FRC loss correlates with loss of both naive CD4 and CD8 T-cell subsets and decreased lymphotoxin-β, a key factor for maintenance of FRC network, we hypothesized that loss of naive T cells is responsible for loss of the FRC network. To test this hypothesis, we assessed the consequences of antibody-mediated depletion of CD4 and CD8 T cells in rhesus macaques and sooty mangabeys. We found that only CD4 T-cell depletion resulted in FRC loss in both species and that this loss was caused by decreased lymphotoxin-β mainly produced by the CD4 T cells. We further found the same dependence of the FRC network on CD4 T cells in HIV-1-infected patients before and after antiretroviral therapy and in other immunodeficiency conditions, such as CD4 depletion in cancer patients induced by chemotherapy and irradiation. CD4 T cells thus play a central role in the maintenance of lymphoid tissue structure necessary for their own homeostasis and reconstitution.

  2. IgD class switching is initiated by microbiota and limited to mucosa-associated lymphoid tissue in mice.

    PubMed

    Choi, Jin Huk; Wang, Kuan-Wen; Zhang, Duanwu; Zhan, Xiaowei; Wang, Tao; Bu, Chun-Hui; Behrendt, Cassie L; Zeng, Ming; Wang, Ying; Misawa, Takuma; Li, Xiaohong; Tang, Miao; Zhan, Xiaoming; Scott, Lindsay; Hildebrand, Sara; Murray, Anne R; Moresco, Eva Marie Y; Hooper, Lora V; Beutler, Bruce

    2017-02-14

    Class-switch recombination (CSR) alters the Ig isotype to diversify antibody effector functions. IgD CSR is a rare event, and its regulation is poorly understood. We report that deficiency of 53BP1, a DNA damage-response protein, caused age-dependent overproduction of secreted IgD resulting from increased IgD CSR exclusively within B cells of mucosa-associated lymphoid tissues. IgD overproduction was dependent on activation-induced cytidine deaminase, hematopoietic MyD88 expression, and an intact microbiome, against which circulating IgD, but not IgM, was reactive. IgD CSR occurred via both alternative nonhomologous end-joining and homologous recombination pathways. Microbiota-dependent IgD CSR also was detected in nasal-associated lymphoid tissue of WT mice. These results identify a pathway, present in WT mice and hyperactivated in 53BP1-deficient mice, by which microbiota signal via Toll-like receptors to elicit IgD CSR.

  3. Ocular adnexal IgG4-producing mucosa-associated lymphoid tissue lymphoma mimicking IgG4-related disease.

    PubMed

    Sato, Yasuharu; Ohshima, Koh-Ichi; Takata, Katsuyoshi; Huang, Xingang; Cui, Wei; Ohno, Kyotaro; Yoshino, Tadashi

    2012-01-01

    IgG4-related disease is a recently proposed clinical entity with several unique clinicopathological features. A chronic inflammatory state with marked fibrosis, which can often be mistaken for malignancy, especially by clinical imaging analyses, unifies these features. In the present report, we describe a case of IgG4-producing mucosa-associated lymphoid tissue lymphoma mimicking IgG4-related disease. The patient was a 55-year-old male who was being followed for right orbital tumor over 1.5 years. The lesion had recently increased in size, so a biopsy was performed. Histologically, the lesion was consistent with IgG4-related disease ; however, IgG4+ plasma cells showed immunoglobulin light-chain restriction and immunoglobulin heavy chain gene rearrangement was detected in the lesion. Therefore, the lesion was diagnosed as IgG4-producing mucosa-associated lymphoid tissue lymphoma. In conclusion, in histological diagnosis of IgG4-related disease, it is important to examine not only IgG4-immunostain but also immunoglobulin light-chain restriction.

  4. Expression of sialyl-Lewis X, an E-selectin ligand, in inflammation, immune processes, and lymphoid tissues.

    PubMed Central

    Munro, J. M.; Lo, S. K.; Corless, C.; Robertson, M. J.; Lee, N. C.; Barnhill, R. L.; Weinberg, D. S.; Bevilacqua, M. P.

    1992-01-01

    The carbohydrate structure sialyl-Lewis X (SLex) can function as a ligand for E-selectin, formerly known as endothelial leukocyte adhesion molecule-1 (ELAM-1). This study was performed to analyze the expression of SLex by leukocytes and other cell types in the context of inflammatory and immune processes. Human peripheral blood cells were examined by flow cytometry using monoclonal antibody CSLEX1 directed against SLex. Cell surface SLex was found in abundance on nearly all isolated polymorphonuclear leukocytes (PMN) and monocytes, and at low levels on a substantial portion (up to 40%) of natural killer cells. This moiety was expressed also on approximately 10% of peripheral blood T cells. Immunohistochemistry was performed on various human tissues involved in inflammatory or immune processes and on secondary lymphoid tissues. In acute appendicitis, endothelial cells of postcapillary venules expressed E-selectin, and most PMN, both within vessels and extravasated, expressed SLex. A substantial number of monocytes/macrophages in inflamed appendiceal, synovial, and dermal tissues also reacted with antibody CSLEX1; however, only rare tissue macrophages in uninflamed nonlymphoid sites showed expression of SLex. These observations are consistent with the concept that SLex on circulating PMN and monocytes functions as a ligand for endothelial E-selectin in the development of inflammatory reactions. SLex-positive lymphocytes also were seen, notably, T lymphocytes in inflamed skin. An unexpected finding was that the CSLEX1 antibody also reacted with venular endothelium in certain lymphoid tissues and in inflamed appendix, but not with endothelium in normal appendix. Whether the SLex antigen identified on endothelium represents de novo expression or passive adsorption remains to be determined. Images Figure 2 Figure 3 Figure 4 Figure 5 PMID:1281620

  5. Human Tissue-Resident Memory T Cells Are Defined by Core Transcriptional and Functional Signatures in Lymphoid and Mucosal Sites.

    PubMed

    Kumar, Brahma V; Ma, Wenji; Miron, Michelle; Granot, Tomer; Guyer, Rebecca S; Carpenter, Dustin J; Senda, Takashi; Sun, Xiaoyun; Ho, Siu-Hong; Lerner, Harvey; Friedman, Amy L; Shen, Yufeng; Farber, Donna L

    2017-09-19

    Tissue-resident memory T cells (TRMs) in mice mediate optimal protective immunity to infection and vaccination, while in humans, the existence and properties of TRMs remain unclear. Here, we use a unique human tissue resource to determine whether human tissue memory T cells constitute a distinct subset in diverse mucosal and lymphoid tissues. We identify a core transcriptional profile within the CD69(+) subset of memory CD4(+) and CD8(+) T cells in lung and spleen that is distinct from that of CD69(-) TEM cells in tissues and circulation and defines human TRMs based on homology to the transcriptional profile of mouse CD8(+) TRMs. Human TRMs in diverse sites exhibit increased expression of adhesion and inhibitory molecules, produce both pro-inflammatory and regulatory cytokines, and have reduced turnover compared with circulating TEM, suggesting unique adaptations for in situ immunity. Together, our results provide a unifying signature for human TRM and a blueprint for designing tissue-targeted immunotherapies. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  6. Innate lymphoid cells in secondary lymphoid organs.

    PubMed

    Bar-Ephraïm, Yotam E; Mebius, Reina E

    2016-05-01

    The family of innate lymphoid cells (ILCs) has attracted attention in recent years as its members are important regulators of immunity, while they can also cause pathology. In both mouse and man, ILCs were initially discovered in developing lymph nodes as lymphoid tissue inducer (LTi) cells. These cells form the prototypic members of the ILC family and play a central role in the formation of secondary lymphoid organs (SLOs). In the absence of LTi cells, lymph nodes (LN) and Peyer's Patches (PP) fail to form in mice, although the splenic white pulp can develop normally. Besides LTi cells, the ILC family encompasses helper-like ILCs with functional distinctions as seen by T-helper cells, as well as cytotoxic natural killer (NK) cells. ILCs are still present in adult SLOs where they have been shown to play a role in lymphoid tissue regeneration. Furthermore, ILCs were implicated to interact with adaptive lymphocytes and influence the adaptive immune response. Here, we review the recent literature on the role of ILCs in secondary lymphoid tissue from the formation of SLOs to mature SLOs in adults, during homeostasis and pathology. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Characterization of New Zealand White Rabbit Gut-Associated Lymphoid Tissues and Use as Viral Oncology Animal Model.

    PubMed

    Haines, Robyn A; Urbiztondo, Rebeccah A; Haynes, Rashade A H; Simpson, Elaine; Niewiesk, Stefan; Lairmore, Michael D

    2016-01-01

    Rabbits have served as a valuable animal model for the pathogenesis of various human diseases, including those related to agents that gain entry through the gastrointestinal tract such as human T cell leukemia virus type 1. However, limited information is available regarding the spatial distribution and phenotypic characterization of major rabbit leukocyte populations in mucosa-associated lymphoid tissues. Herein, we describe the spatial distribution and phenotypic characterization of leukocytes from gut-associated lymphoid tissues (GALT) from 12-week-old New Zealand White rabbits. Our data indicate that rabbits have similar distribution of leukocyte subsets as humans, both in the GALT inductive and effector sites and in mesenteric lymph nodes, spleen, and peripheral blood. GALT inductive sites, including appendix, cecal tonsil, Peyer's patches, and ileocecal plaque, had variable B cell/T cell ratios (ranging from 4.0 to 0.8) with a predominance of CD4 T cells within the T cell population in all four tissues. Intraepithelial and lamina propria compartments contained mostly T cells, with CD4 T cells predominating in the lamina propria compartment and CD8 T cells predominating in the intraepithelial compartment. Mesenteric lymph node, peripheral blood, and splenic samples contained approximately equal percentages of B cells and T cells, with a high proportion of CD4 T cells compared with CD8 T cells. Collectively, our data indicate that New Zealand White rabbits are comparable with humans throughout their GALT and support future studies that use the rabbit model to study human gut-associated disease or infectious agents that gain entry by the oral route. © The Author 2016. Published by Oxford University Press on behalf of the Institute for Laboratory Animal Research. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  8. Characterization of New Zealand White Rabbit Gut-Associated Lymphoid Tissues and Use as Viral Oncology Animal Model

    PubMed Central

    Haines, Robyn A.; Urbiztondo, Rebeccah A.; Haynes, Rashade A. H.; Simpson, Elaine; Niewiesk, Stefan; Lairmore, Michael D.

    2016-01-01

    Rabbits have served as a valuable animal model for the pathogenesis of various human diseases, including those related to agents that gain entry through the gastrointestinal tract such as human T cell leukemia virus type 1. However, limited information is available regarding the spatial distribution and phenotypic characterization of major rabbit leukocyte populations in mucosa-associated lymphoid tissues. Herein, we describe the spatial distribution and phenotypic characterization of leukocytes from gut-associated lymphoid tissues (GALT) from 12-week-old New Zealand White rabbits. Our data indicate that rabbits have similar distribution of leukocyte subsets as humans, both in the GALT inductive and effector sites and in mesenteric lymph nodes, spleen, and peripheral blood. GALT inductive sites, including appendix, cecal tonsil, Peyer's patches, and ileocecal plaque, had variable B cell/T cell ratios (ranging from 4.0 to 0.8) with a predominance of CD4 T cells within the T cell population in all four tissues. Intraepithelial and lamina propria compartments contained mostly T cells, with CD4 T cells predominating in the lamina propria compartment and CD8 T cells predominating in the intraepithelial compartment. Mesenteric lymph node, peripheral blood, and splenic samples contained approximately equal percentages of B cells and T cells, with a high proportion of CD4 T cells compared with CD8 T cells. Collectively, our data indicate that New Zealand White rabbits are comparable with humans throughout their GALT and support future studies that use the rabbit model to study human gut-associated disease or infectious agents that gain entry by the oral route. PMID:27034393

  9. Mucosa-associated lymphoid tissue lymphoma with unusual 18F-FDG hypermetabolism arising at the colorectal anastomosis

    PubMed Central

    Zhang, Na-Sha; Shi, Fang; Kong, Li; Zhu, Hui

    2017-01-01

    Mucosa-associated lymphoid tissue (MALT) lymphoma usually originates from the stomach and presents with low 18F-fluorodeoxyglucose (FDG) avidity with average maximum standard uptake value of 3.6. Colorectal MALT lymphoma is a rare entity that contributes to 1.6% of all MALT lymphomas and < 0.2% of large intestinal malignancies. The case reported herein firstly revealed stage IIE MALT lymphoma with unexpected higher 18F-FDG avidity of 18.9 arising at the colorectal anastomosis in a patient with a surgical history for sigmoid adenocarcinoma, which was strongly suspected as local recurrence before histopathological and immunohistochemical examinations. After accurate diagnosis, the patient received four cycles of standard R-CVP regimen (rituximab, cyclophosphamide, vincristine and prednisone), combined target therapy and chemotherapy, instead of radiotherapy recommended by National Comprehensive Cancer Network guidelines. He tolerated the treatment well and reached complete remission. PMID:28210093

  10. Collision tumor: invasive ductal carcinoma in association with mucosa-associated lymphoid tissue (MALT) lymphoma in the same breast.

    PubMed

    Quilon, Joanne M; Gaskin, Thomas A; Ludwig, Arthur S; Alley, Catherine

    2006-02-01

    Synchronous occurrence of multiple neoplastic processes is uncommon and the relationship between breast cancer with lymphoproliferative diseases is unusual as well. Furthermore, breast involvement by malignant lymphoma is a rare event and primary breast mucosa-associated lymphoid tissue (MALT) lymphoma is even rarer. We report a patient with synchronous occurrence of malignant lymphoma of MALT type and ductal carcinoma of the breast, presenting as "collision tumor," invading each other and occurring as a single mass in the breast. Involvement of the sentinel lymph node by MALT lymphoma was demonstrated with no evidence of metastatic carcinoma. Staging bone marrow biopsy did not show involvement by malignant lymphoma or carcinoma. Our patient was treated with chemotherapy for the lymphoma. She also received radiotherapy and aromatase inhibitor as adjuvant therapy for the breast carcinoma.

  11. Isolated Follicles Enriched for Centroblasts and Lacking t(14;18)/BCL2 in Lymphoid Tissue: Diagnostic and Clinical Implications

    PubMed Central

    Gratzinger, Dita; Jones, Carol D.; Zehnder, James L.; Bangs, Charles D.; Cherry, Athena; Warnke, Roger A.; Natkunam, Yasodha

    2016-01-01

    We sought to address the significance of isolated follicles that exhibit atypical morphologic features that may be mistaken for lymphoma in a background of reactive lymphoid tissue. Seven cases that demonstrated centroblast-predominant isolated follicles and absent BCL2 staining in otherwise-normal lymph nodes were studied. Four of seven cases showed clonal B-cell proliferations amid a polyclonal B cell background; all cases lacked the IGH-BCL2 translocation and BCL2 protein expression. Although three patients had invasive breast carcinoma at other sites, none were associated with systemic lymphoma up to 44 months after diagnosis. The immunoarchitectural features of these highly unusual cases raise the question of whether a predominance of centroblasts and/or absence of BCL2 expression could represent a precursor lesion or atypical reactive phenomenon. Differentiating such cases from follicular lymphoma or another mimic is critical, lest patients with indolent proliferations be exposed to unnecessarily aggressive treatment. PMID:26991267

  12. Novel concept of iSALT (inducible skin-associated lymphoid tissue) in the elicitation of allergic contact dermatitis

    PubMed Central

    HONDA, Tetsuya; KABASHIMA, Kenji

    2016-01-01

    Allergic contact dermatitis (ACD) is one of the most common inflammatory skin diseases, which is classified as a delayed-type hypersensitivity immune response. The development of ACD is divided into two phases: sensitization and elicitation. In the sensitization phase, antigen-specific effector T cells are induced in the draining lymph nodes by antigen-captured cutaneous dendritic cells (DCs) that migrate from the skin. In the elicitation phase, the effector T cells are activated in the skin by antigen-captured cutaneous DCs and produce various chemical mediators, which create antigen-specific inflammation. In this review, we discuss the recent advancements in the immunological mechanisms of ACD, focusing on the mechanisms in the elicitation phase. The observations of elicitation of CHS lead to the emerging novel concept of iSALT (inducible skin-associated lymphoid tissue). PMID:26755397

  13. Epithelial-stromal interaction via Notch signaling is essential for the full maturation of gut-associated lymphoid tissues.

    PubMed

    Obata, Yuuki; Kimura, Shunsuke; Nakato, Gaku; Iizuka, Keito; Miyagawa, Yurika; Nakamura, Yutaka; Furusawa, Yukihiro; Sugiyama, Machiko; Suzuki, Keiichiro; Ebisawa, Masashi; Fujimura, Yumiko; Yoshida, Hisahiro; Iwanaga, Toshihiko; Hase, Koji; Ohno, Hiroshi

    2014-12-01

    Intrinsic Notch signaling in intestinal epithelial cells restricts secretory cell differentiation. In gut-associated lymphoid tissue (GALT), stromal cells located beneath the follicle-associated epithelium (FAE) abundantly express the Notch ligand delta-like 1 (Dll1). Here, we show that mice lacking Rbpj-a gene encoding a transcription factor implicated in Notch signaling-in intestinal epithelial cells have defective GALT maturation. This defect can be attributed to the expansion of goblet cells, which leads to the down-regulation of CCL20 in FAE. These data demonstrate that epithelial Notch signaling maintained by stromal cells contributes to the full maturation of GALT by restricting secretory cell differentiation in FAE.

  14. Bilateral Bronchiectasis as a Presentation Form of Pulmonary Marginal Zone B-Cell Lymphoma of Bronchus Associated Lymphoid Tissue

    PubMed Central

    Ernst, Glenda; Torres, Carla; Borsini, Eduardo; Vigovich, Félix; Downey, Daniel; Salvado, Alajandro; Bosio, Martín

    2015-01-01

    The pulmonary marginal zone B-cell lymphoma of bronchus associated lymphoid tissue of the lung (BALT) is a rare illness that can remain without symptoms. Radiological findings of pulmonary lymphoma are heterogeneous. In literature, bronchiectasis is only described in one patient who also had besides adenomegalies. We reported on a 48-year-old female patient. She showed symptoms consistent with dyspnea with productive cough; there were crepitant sounds in the auscultation. Pulmonary functional test has shown a severe restrictive pattern with a low FVC and DLCO. CT scan showed bronchiectasis in the medium lobule without adenomegalies. Echocardiogram was normal, and the laboratory findings only showed leukocytosis. There were no findings in the bronchoscopy, but the lung biopsy showed a B-cell pulmonary lymphoma (positive to CD20 and CD79a in immunostaining). A wide variety of radiological manifestations has been previously described; however, we have presented this rare case, with bronchiectasis, as unique radiological finding. PMID:26839723

  15. The effect of PrP(Sc) accumulation on inflammatory gene expression within sheep peripheral lymphoid tissue.

    PubMed

    Gossner, Anton G; Hopkins, John

    2015-12-31

    Accumulation of the misfolded prion protein, PrP(Sc) in the central nervous system (CNS) is strongly linked to progressive neurodegenerative disease. For many transmissible spongiform encephalopathies (TSEs), peripheral lymphoid tissue is an important site of PrP(Sc) amplification but without gross immunological consequence. Susceptible VRQ homozygous New Zealand Cheviot sheep were infected with SSBP/1 scrapie by inoculation in the drainage area of the prescapular lymph nodes. The earliest time that PrP(Sc) was consistently detected by immunohistology in these nodes was D50 post infection. This transcriptomic study of lymph node taken before (D10) and after (D50) the detection of PrP(Sc), aimed to identify the genes and physiological pathways affected by disease progression within the nodes as assessed by PrP(Sc) detection. Affymetrix Ovine Gene arrays identified 75 and 80 genes as differentially-expressed at D10 and D50, respectively, in comparison with control sheep inoculated with uninfected brain homogenate. Approximately 70% of these were repressed at each time point. RT-qPCR analysis of seven genes showed statistically significant correlation with the array data, although the results for IL1RN and TGIF were different between the two technologies. The ingenuity pathway analysis (IPA) and general low level of repression of gene expression in lymphoid tissue, including many inflammatory genes, contrasts with the pro-inflammatory and pro-apoptotic events that occur within the CNS at equivalent stages of disease progression as assessed by PrP(Sc) accumulation.

  16. CD4 and MHC class I down-modulation activities of nef alleles from brain- and lymphoid tissue-derived primary HIV-1 isolates

    PubMed Central

    Gray, Lachlan R.; Gabuzda, Dana; Cowley, Daniel; Ellett, Anne; Chiavaroli, Lisa; Wesselingh, Steven L.; Churchill, Melissa J.; Gorry, Paul R.

    2015-01-01

    HIV-1 nef undergoes adaptive evolution in the CNS, reflecting altered requirements for HIV-1 replication in macrophages/microglia and brain-specific immune selection pressures. The role of Nef in HIV-1 neurotropism and the pathogenesis of HIV-associated dementia (HAD) is unclear. In this study, we characterized 82 nef alleles cloned from brain, CSF, spinal cord and blood/lymphoid tissue-derived HIV-1 isolates from 7 subjects with HAD. CNS isolate-derived nef alleles were genetically compartmentalized and had reduced sequence diversity compared to those from lymphoid tissue isolates. Defective nef alleles predominated in a brain-derived isolate from one of the 7 subjects (MACS2-br). The ability of Nef to down-modulate CD4 and MHC class 1 (MHC-1) was generally conserved among nef alleles from both CNS and lymphoid tissues. However, the potency of CD4 and MHC-1 down-modulation was variable, which was associated with sequence alterations known to influence these Nef functions. These results suggest that CD4 and MHC-1 down-modulation are highly conserved functions among nef alleles from CNS- and lymphoid tissue-derived HIV-1 isolates that may contribute to viral replication and escape from immune surveillance in the CNS. PMID:21165790

  17. Retention of Ag-specific memory CD4(+) T cells in the draining lymph node indicates lymphoid tissue resident memory populations.

    PubMed

    Marriott, Clare L; Dutton, Emma E; Tomura, Michio; Withers, David R

    2017-05-01

    Several different memory T-cell populations have now been described based upon surface receptor expression and migratory capabilities. Here we have assessed murine endogenous memory CD4(+) T cells generated within a draining lymph node and their subsequent migration to other secondary lymphoid tissues. Having established a model response targeting a specific peripheral lymph node, we temporally labelled all the cells within draining lymph node using photoconversion. Tracking of photoconverted and non-photoconverted Ag-specific CD4(+) T cells revealed the rapid establishment of a circulating memory population in all lymph nodes within days of immunisation. Strikingly, a resident memory CD4(+) T cell population became established in the draining lymph node and persisted for several months in the absence of detectable migration to other lymphoid tissue. These cells most closely resembled effector memory T cells, usually associated with circulation through non-lymphoid tissue, but here, these cells were retained in the draining lymph node. These data indicate that lymphoid tissue resident memory CD4(+) T-cell populations are generated in peripheral lymph nodes following immunisation. © 2017 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Epstein-Barr Virus–induced Molecule 1 Ligand Chemokine Is Expressed by Dendritic Cells in Lymphoid Tissues and Strongly Attracts Naive T Cells and Activated B Cells

    PubMed Central

    Ngo, Vu N.; Lucy Tang, H.; Cyster, Jason G.

    1998-01-01

    Movement of T and B lymphocytes through secondary lymphoid tissues is likely to involve multiple cues that help the cells navigate to appropriate compartments. Epstein-Barr virus– induced molecule 1 (EBI-1) ligand chemokine (ELC/MIP3β) is expressed constitutively within lymphoid tissues and may act as such a guidance cue. Here, we have isolated mouse ELC and characterized its expression pattern and chemotactic properties. ELC is expressed constitutively in dendritic cells within the T cell zone of secondary lymphoid tissues. Recombinant ELC was strongly chemotactic for naive (L-selectinhi) CD4 T cells and for CD8 T cells and weakly attractive for resting B cells and memory (L-selectinlo) CD4 T cells. After activation through the B cell receptor, the chemotactic response of B cells was enhanced. Like its human counterpart, murine ELC stimulated cells transfected with EBI-1/CC chemokine receptor 7 (CCR7). Our findings suggest a central role for ELC in promoting encounters between recirculating T cells and dendritic cells and in the migration of activated B cells into the T zone of secondary lymphoid tissues. PMID:9653094

  19. Epstein-Barr virus-induced molecule 1 ligand chemokine is expressed by dendritic cells in lymphoid tissues and strongly attracts naive T cells and activated B cells.

    PubMed

    Ngo, V N; Tang, H L; Cyster, J G

    1998-07-06

    Movement of T and B lymphocytes through secondary lymphoid tissues is likely to involve multiple cues that help the cells navigate to appropriate compartments. Epstein-Barr virus- induced molecule 1 (EBI-1) ligand chemokine (ELC/MIP3beta) is expressed constitutively within lymphoid tissues and may act as such a guidance cue. Here, we have isolated mouse ELC and characterized its expression pattern and chemotactic properties. ELC is expressed constitutively in dendritic cells within the T cell zone of secondary lymphoid tissues. Recombinant ELC was strongly chemotactic for naive (L-selectinhi) CD4 T cells and for CD8 T cells and weakly attractive for resting B cells and memory (L-selectinlo) CD4 T cells. After activation through the B cell receptor, the chemotactic response of B cells was enhanced. Like its human counterpart, murine ELC stimulated cells transfected with EBI-1/CC chemokine receptor 7 (CCR7). Our findings suggest a central role for ELC in promoting encounters between recirculating T cells and dendritic cells and in the migration of activated B cells into the T zone of secondary lymphoid tissues.

  20. Gastric marginal zone lymphoma of mucosa-associated lymphoid tissue and signet ring cell carcinoma, synchronous collision tumour of the stomach: a case report.

    PubMed

    George, Smiley Annie; Junaid, T A

    2014-01-01

    To report a rare case of synchronous marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) signet ring cell carcinoma occurring as a collision tumour in the stomach. A 53-year-old man was diagnosed initially with signet ring cell carcinoma of the stomach. The microscopy of the subsequent total gastrectomy revealed a collision tumour of MALT lymphoma and signet ring cell carcinoma associated with Helicobacter pylori gastritis. This case highlighted the importance of a careful evaluation of the accompanying lymphoid population in the biopsy samples of gastric adenocarcinoma and underlined the need for multiple endoscopic biopsies to detect these rare synchronous tumours. © 2013 S. Karger AG, Basel.

  1. Reciprocal regulation of lymphoid tissue development in the large intestine by IL-25 and IL-23

    PubMed Central

    Donaldson, D S; Bradford, B M; Artis, D; Mabbott, N A

    2015-01-01

    Isolated lymphoid follicles (ILFs) develop after birth in the small and large intestines (SI and LI) and represent a dynamic response of the gut immune system to the microbiota. Despite their similarities, ILF development in the SI and LI differs on a number of levels. We show that unlike ILF in the SI, the microbiota inhibits ILF development in the colon as conventionalization of germ-free mice reduced colonic ILFs. From this, we identified a novel mechanism regulating colonic ILF development through the action of interleukin (IL)-25 on IL-23 and its ability to modulate T regulatory cell (Treg) differentiation. Colonic ILF develop in the absence of a number of factors required for the development of their SI counterparts and can be specifically suppressed by factors other than IL-25. However, IL-23 is the only factor identified that specifically promotes colonic ILFs without affecting SI-ILF development. Both IL-23 and ILFs are associated with inflammatory bowel disease, suggesting that disruption to this pathway may have an important role in the breakdown of microbiota-immune homeostasis. PMID:25249168

  2. Reciprocal regulation of lymphoid tissue development in the large intestine by IL-25 and IL-23.

    PubMed

    Donaldson, D S; Bradford, B M; Artis, D; Mabbott, N A

    2015-05-01

    Isolated lymphoid follicles (ILFs) develop after birth in the small and large intestines (SI and LI) and represent a dynamic response of the gut immune system to the microbiota. Despite their similarities, ILF development in the SI and LI differs on a number of levels. We show that unlike ILF in the SI, the microbiota inhibits ILF development in the colon as conventionalization of germ-free mice reduced colonic ILFs. From this, we identified a novel mechanism regulating colonic ILF development through the action of interleukin (IL)-25 on IL-23 and its ability to modulate T regulatory cell (Treg) differentiation. Colonic ILF develop in the absence of a number of factors required for the development of their SI counterparts and can be specifically suppressed by factors other than IL-25. However, IL-23 is the only factor identified that specifically promotes colonic ILFs without affecting SI-ILF development. Both IL-23 and ILFs are associated with inflammatory bowel disease, suggesting that disruption to this pathway may have an important role in the breakdown of microbiota-immune homeostasis.

  3. CSF1R Protein Expression in Reactive Lymphoid Tissues and Lymphoma: Its Relevance in Classical Hodgkin Lymphoma.

    PubMed

    Martín-Moreno, Ana M; Roncador, Giovanna; Maestre, Lorena; Mata, Elena; Jiménez, Scherezade; Martínez-Torrecuadrada, Jorge L; Reyes-García, Ana I; Rubio, Carmen; Tomás, José F; Estévez, Mónica; Pulford, Karen; Piris, Miguel A; García, Juan F

    2015-01-01

    Tumour-associated macrophages (TAMs) have been associated with survival in classic Hodgkin lymphoma (cHL) and other lymphoma types. The maturation and differentiation of tissue macrophages depends upon interactions between colony-stimulating factor 1 receptor (CSF1R) and its ligands. There remains, however, a lack of consistent information on CSF1R expression in TAMs. A new monoclonal antibody, FER216, was generated to investigate CSF1R protein distribution in formalin fixed tissue samples from 24 reactive lymphoid tissues and 187 different lymphoma types. We also analysed the distribution of CSF1R+, CD68+ and CD163+ macrophages by double immunostaining, and studied the relationship between CSF1R expression and survival in an independent series of 249 cHL patients. CSF1R+ TAMs were less frequent in B-cell lymphocytic leukaemia and lymphoblastic B-cell lymphoma than in diffuse large B-cell lymphoma, peripheral T-cell lymphoma, angioimmunoblastic T-cell lymphoma and cHL. HRS cells in cHL and, with the exception of three cases of anaplastic large cell lymphoma, the neoplastic cells in NHLs, lacked detectable CSF1R protein. A CSF1R+ enriched microenvironment in cHL was associated with shorter survival in an independent series of 249 cHL patients. CSF1R pathway activation was evident in the cHL and inactivation of this pathway could be a potential therapeutic target in cHL cases.

  4. CSF1R Protein Expression in Reactive Lymphoid Tissues and Lymphoma: Its Relevance in Classical Hodgkin Lymphoma

    PubMed Central

    Maestre, Lorena; Mata, Elena; Jiménez, Scherezade; Martínez-Torrecuadrada, Jorge L.; Reyes-García, Ana I.; Rubio, Carmen; Tomás, José F.; Estévez, Mónica; Pulford, Karen; Piris, Miguel A.; García, Juan F.

    2015-01-01

    Tumour-associated macrophages (TAMs) have been associated with survival in classic Hodgkin lymphoma (cHL) and other lymphoma types. The maturation and differentiation of tissue macrophages depends upon interactions between colony-stimulating factor 1 receptor (CSF1R) and its ligands. There remains, however, a lack of consistent information on CSF1R expression in TAMs. A new monoclonal antibody, FER216, was generated to investigate CSF1R protein distribution in formalin fixed tissue samples from 24 reactive lymphoid tissues and 187 different lymphoma types. We also analysed the distribution of CSF1R+, CD68+ and CD163+ macrophages by double immunostaining, and studied the relationship between CSF1R expression and survival in an independent series of 249 cHL patients. CSF1R+ TAMs were less frequent in B-cell lymphocytic leukaemia and lymphoblastic B-cell lymphoma than in diffuse large B-cell lymphoma, peripheral T-cell lymphoma, angioimmunoblastic T-cell lymphoma and cHL. HRS cells in cHL and, with the exception of three cases of anaplastic large cell lymphoma, the neoplastic cells in NHLs, lacked detectable CSF1R protein. A CSF1R+ enriched microenvironment in cHL was associated with shorter survival in an independent series of 249 cHL patients. CSF1R pathway activation was evident in the cHL and inactivation of this pathway could be a potential therapeutic target in cHL cases. PMID:26066800

  5. Immunobiotic Lactobacillus strains augment NLRP3 expression in newborn and adult porcine gut-associated lymphoid tissues.

    PubMed

    Tohno, Masanori; Shimosato, Takeshi; Aso, Hisashi; Kitazawa, Haruki

    2011-12-15

    We isolated cDNA encoding porcine nucleotide-binding domain-like receptor family, pryin domain containing 3 (NLRP3) from Peyer's patches. The complete nucleotide open reading frame of porcine NLRP3 contains 3108-bp encoding a deduced polypeptide of 1036-amino acid residues. The porcine NLRP3 amino acid sequence is more similar to the longest isoform of human than the mouse counterpart. The predicted amino acid sequence of porcine NLRP3 presented nine C-terminal leucine-rich repeat domains. In newborn swine, the expression of NLRP3 was detected at higher levels in spleen and mesenteric lymph nodes, while lower levels were observed in intestinal tissues. In adult swine, NLRP3 was strongly expressed in Peyer's patches and the mesenteric lymph nodes, and the expression level in the lower intestinal tissues was comparable to that in spleen. Toll-like receptor and nucleotide-binding domain ligands, as well as Lactobacillus delbrueckii subsp. bulgaricus and Lactobacillus gasseri, enhanced NLRP3 expression in gut-associated lymphoid tissues (GALT) of newborn and adult swine. Our results should aid in understanding the intestinal immunoregulatory mechanisms underlying NLRP3 activation and the priming ability of immunobiotic lactic acid bacteria in porcine GALT.

  6. The effect of deoxyribonucleic acid extraction methods from lymphoid tissue on the purity, content, and amplifying ability

    PubMed Central

    Ayatollahi, Hossein; Sadeghian, Mohammad Hadi; Keramati, Mohammad Reza; Ayatollahi, Ali; Shajiei, Arezoo; Sheikhi, Maryam; Bakhshi, Samane

    2016-01-01

    Background: Nowadays, definitive diagnosis of numerous diseases is based on the genetic and molecular findings. Therefore, preparation of fundamental materials for these evaluations is necessary. Deoxyribonucleic acid (DNA) is the first material for the molecular pathology and genetic analysis, and better results need more pure DNA. Furthermore, higher concentration of achieved DNA causes better results and higher amplifying ability for subsequent steps. We aim to evaluate five DNA extraction methods to compare DNA intimacy including purity, concentration, and amplifying ability with each other. Materials and Methods: The lymphoid tissue DNA was extracted from formalin-fixed, paraffin embedded (FFPE) tissue through five different methods including phenol-chloroform as the reference method, DNA isolation kit (QIAamp DNA FFPE Tissue Kit, Qiagen, Germany), proteinase K and xylol extraction and heat alkaline plus mineral oil extraction as authorship innovative method. Finally, polymerase chain reaction (PCR) and real-time PCR method were assessed to compare each following method consider to DNA purity and its concentration. Results: Among five different applied methods, the highest mean of DNA purity was related to heat alkaline method. Moreover, the highest mean of DNA concentration was related to heat alkaline plus mineral oil. Furthermore, the best result in quantitative PCR was in proteinase K method that had the lowest cycle threshold averages among the other extraction methods. Conclusion: We concluded that our innovative method for DNA extraction (heat alkaline plus mineral oil) achieved high DNA purity and concentration. PMID:27630381

  7. Prevalence of Achromobacter xylosoxidans in pulmonary mucosa-associated lymphoid tissue lymphoma in different regions of Europe.

    PubMed

    Adam, Patrick; Czapiewski, Piotr; Colak, Seba; Kosmidis, Perikles; Tousseyn, Thomas; Sagaert, Xavier; Boudova, Ludmila; Okoń, Krzysztof; Morresi-Hauf, Alicia; Agostinelli, Claudio; Pileri, Stefano; Pruneri, Giancarlo; Martinelli, Giovanni; Du, Ming-Qing; Fend, Falko

    2014-03-01

    Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) comprises 7-8% of B-cell lymphomas and commonly originates from a background of long-standing chronic inflammation. An association with distinct bacteria species has been confirmed for several anatomical sites of MALT lymphoma. For pulmonary MALT lymphoma, however, a clear link with an infectious agent or autoimmune disorder has not yet been reported. Using a 16S rRNA gene-based approach, we have recently identified Achromobacter (Alcaligenes) xylosoxidans in eight of nine cases of pulmonary MALT lymphoma. A. xylosoxidans is a gram-negative betaproteobacterium with low virulence, but high resistance to antibiotic treatment. To further examine a potential association with A. xylosoxidans, 124 cases of pulmonary MALT lymphoma and 82 control tissues from six European countries were analysed using a specific nested PCR. Although prevalence rates for A. xylosoxidans varied significantly from country to country, they were consistently higher for MALT lymphoma as compared to controls. Overall, 57/124 (46%) pulmonary MALT lymphomas and 15/82 (18%) control tissues were positive for A. xylosoxidans (P = 0·004). Whether the significant association of A. xylosoxidans with pulmonary MALT lymphoma demonstrated in our study points to a potential causal role in the pathogenesis of this lymphoma will require further studies. © 2013 John Wiley & Sons Ltd.

  8. Milky spots in the omentum develop in the absence of lymphoid tissue inducer cells and independently support B and T cell responses to peritoneal antigens

    PubMed Central

    Rangel-Moreno, Javier; Moyron-Quiroz, Juan E.; Carragher, Damian M.; Kusser, Kim; Hartson, Louise; Moquin, Amy; Randall, Troy D.

    2009-01-01

    Summary The omentum is a site of B1 lymphopoiesis and immune responsiveness to T-independent antigens. However, it is unknown whether it supports immune responses independently of conventional lymphoid organs. We show that the omentum collects antigens and cells from the peritoneal cavity and supports T-dependent B cell responses, including isotype switching, somatic hypermutation and limited affinity maturation, despite the lack of identifiable follicular dendritic cells. The omentum also supports CD4 and CD8 responses to peritoneal antigens and recruits effector T cells primed in other locations. Unlike conventional lymphoid organs, milky spots in the omentum develop in the absence of lymphoid tissue inducer cells, but require CXCL13. Although the lymphoid architecture of milky spots is disrupted in lymphotoxin-deficient mice, normal architecture is restored by reconstitution with lymphotoxin-sufficient hematopoietic cells. These results indicate that the milky spots of the omentum function as unique secondary lymphoid organs that promote immunity to peritoneal antigens. PMID:19427241

  9. Preparation and characterization of anti-HIV nanodrug targeted to microfold cell of gut-associated lymphoid tissue

    PubMed Central

    Roy, Upal; Ding, Hong; Pilakka-Kanthikeel, Sudheesh; Raymond, Andrea D; Atluri, Venkata; Yndart, Adriana; Kaftanovskaya, Elena M; Batrakova, Elena; Agudelo, Marisela; Nair, Madhavan

    2015-01-01

    The human immunodeficiency virus 1 (HIV-1) still remains one of the leading life-threatening diseases in the world. The introduction of highly active antiretroviral therapy has significantly reduced disease morbidity and mortality. However, most of the drugs have variable penetrance into viral reservoir sites, including gut-associated lymphoid tissue (GALT). Being the largest lymphoid organ, GALT plays a key role in early HIV infection and host–pathogen interaction. Many different treatment options have been proposed to eradicate the virus from GALT. However, it becomes difficult to deliver traditional drugs to the GALT because of its complex physiology. In this regard, we developed a polymer-based Pluronic nanocarrier containing anti-HIV drug called efavirenz (EFV) targeting Microfold cells (M-cells) in the GALT. M-cells are specialized epithelial cells that are predominantly present in the GALT. In this work, we have exploited this paracellular transport property of M-cells for targeted delivery of Pluronic nanocarrier tagged EFV, bioconjugated with anti-M-cell-specific antibodies to the GALT (nanodrug). Preliminary characterization showed that the nanodrug (EFV-F12-COOH) is of 140 nm size with 0.3 polydispersion index, and the zeta potential of the particles was −19.38±2.2 mV. Further, drug dissolution study has shown a significantly improved sustained release over free drugs. Binding potential of nanodrug with M-cell was also confirmed with fluorescence microscopy and in vitro uptake and release studies. The anti-HIV activity of the nanodrug was also significantly higher compared to that of free drug. This novel formulation was able to show sustained release of EFV and inhibit the HIV-1 infection in the GALT compared to the free drug. The present study has potential for our in vivo targeted nanodrug delivery system by combining traditional enteric-coated capsule technique via oral administration. PMID:26425084

  10. The Transcriptomic and Proteomic Landscapes of Bone Marrow and Secondary Lymphoid Tissues

    PubMed Central

    Andersson, Sandra; Nilsson, Kenneth; Fagerberg, Linn; Hallström, Björn M.; Sundström, Christer; Danielsson, Angelika; Edlund, Karolina; Uhlen, Mathias; Asplund, Anna

    2014-01-01

    Background The sequencing of the human genome has opened doors for global gene expression profiling, and the immense amount of data will lay an important ground for future studies of normal and diseased tissues. The Human Protein Atlas project aims to systematically map the human gene and protein expression landscape in a multitude of normal healthy tissues as well as cancers, enabling the characterization of both housekeeping genes and genes that display a tissue-specific expression pattern. This article focuses on identifying and describing genes with an elevated expression in four lymphohematopoietic tissue types (bone marrow, lymph node, spleen and appendix), based on the Human Protein Atlas-strategy that combines high throughput transcriptomics with affinity-based proteomics. Results An enriched or enhanced expression in one or more of the lymphohematopoietic tissues, compared to other tissue-types, was seen for 693 out of 20,050 genes, and the highest levels of expression were found in bone marrow for neutrophilic and erythrocytic genes. A majority of these genes were found to constitute well-characterized genes with known functions in lymphatic or hematopoietic cells, while others are not previously studied, as exemplified by C19ORF59. Conclusions In this paper we present a strategy of combining next generation RNA-sequencing with in situ affinity-based proteomics in order to identify and describe new gene targets for further research on lymphatic or hematopoietic cells and tissues. The results constitute lists of genes with enriched or enhanced expression in the four lymphohematopoietic tissues, exemplified also on protein level with immunohistochemical images. PMID:25541736

  11. Delayed Efficacy After Treatment With Lenalidomide or Thalidomide in Patients With Mucosa-Associated Lymphoid Tissue Lymphoma

    PubMed Central

    Kiesewetter, Barbara; Troch, Marlene; Mayerhoefer, Marius E.; Dolak, Werner; Simonitsch-Klupp, Ingrid

    2016-01-01

    Background. The immunomodulatory drugs (IMiDs) thalidomide and lenalidomide have both been tested for treatment of mucosa-associated lymphoid tissue (MALT) lymphoma, with lenalidomide, in particular, showing promising activity. However, long-term results are missing. Because of the late-onset remissions registered in individual patients, we have systemically analyzed the patients treated with IMiDs at our institution for long-term results. Methods. Within the present retrospective analysis, we identified 25 patients who had been treated with lenalidomide (n = 18) or thalidomide (n = 7) and were available for long-term assessments of outcome. All patients were followed up according to a standardized follow-up protocol. Results. Of the 25 patients, 7 (28%) experienced delayed-onset responses without further treatment (thalidomide, n = 2; lenalidomide, n = 5). In 4 patients (16%), the initial outcome switched to a better result (partial remission [PR] to complete remission [CR], n = 1; stable disease [SD] to PR, n = 1; SD to CR, n = 1; and PD to CR, n = 1) after a median time of 19.5 months (range, 10.9–32.0). Furthermore, 2 patients showed ongoing shrinkage of the target lesion for 47.4+ and 43.5+ months, respectively, and 1 patient had durable disease stabilization for 16.2+ months. The median time to the best response for all responding patients (13 of 25; 53%) was 7.3 months (interquartile range [IQR], 5.6–22.5). After a median follow-up of 46 months (IQR, 32.0–58.5), 23 of 25 patients (92%) were alive. Conclusion. Our findings suggest that late-onset remissions might be a common phenomenon in the use of IMiDs for the treatment of MALT lymphoma. Thus, sufficient follow-up time after treatment before the initiation of further therapy appears crucial to assess the full effect of therapy and avoid unnecessary overtreatment. Implications for Practice: The immunomodulatory drugs (IMiDs) thalidomide and lenalidomide have been tested for the treatment of mucosa

  12. DIET REGULATES THE DEVELOPMENT OF GUT-ASSOCIATED LYMPHOID TISSUE IN NEONATAL PIGLETS

    USDA-ARS?s Scientific Manuscript database

    During the immediate postnatal period tissue growth in the pig gastrointestinal tract increases by up to 80%. Controversy exists concerning diet-induced changes to the gut epithelial and immunocytes that occur during weaning. Comparisons of bovine milk protein digestion in 3-week-old piglets and 3-...

  13. RT-PCR Analysis of RNA Extracted from Bouin-Fixed and Paraffin-Embedded Lymphoid Tissues

    PubMed Central

    Gloghini, Annunziata; Canal, Barbara; Klein, Ulf; Dal Maso, Luigino; Perin, Tiziana; Dalla-Favera, Riccardo; Carbone, Antonino

    2004-01-01

    In the present study, we have investigated whether RNA can be efficiently isolated from Bouin-fixed or formalin-fixed, paraffin-embedded lymphoid tissue specimens. To this aim, we applied a new and simple method that includes the combination of proteinase K digestion and column purification. By this method, we demonstrated that the amplification of long fragments could be accomplished after a pre-heating step before cDNA synthesis associated with the use of enzymes that work at high temperature. By means of PCR using different primers for two examined genes (glyceraldehyde-3-phosphate dehydrogenase [GAPDH]- and CD40), we amplified segments of cDNA obtained by reverse transcription of the isolated RNA extracted from Bouin-fixed or formalin-fixed paraffin-embedded tissues. Amplified fragments of the expected sizes were obtained for both genes tested indicating that this method is suitable for the isolation of high-quality RNA. To explore the possibility for giving accurate real time quantitative RT-PCR results, cDNA obtained from matched frozen, Bouin-fixed and formalin-fixed neoplastic samples (two diffuse large cell lymphomas, one plasmacytoma) was tested for the following target genes: CD40, Aquaporin-3, BLIMP1, IRF4, Syndecan-1. Delta threshold cycle (ΔCT) values for Bouin-fixed and formalin-fixed paraffin-embedded tissues and their correlation with those for frozen samples showed an extremely high correlation (r > 0.90) for all of the tested genes. These results show that the method of RNA extraction we propose is suitable for giving accurate real time quantitative RT-PCR results. PMID:15507667

  14. Expression of complement receptor 2 (CD21), membrane IgM and the inhibitory receptor CD32 (FcgammaRIIb) in the lymphoid tissues of neonatal calves.

    PubMed

    Chattha, Kuldeep S; Firth, Matthew A; Hodgins, Douglas C; Shewen, Patricia E

    2010-09-15

    Limited active antibody responses in neonates following vaccination have been attributed to immaturity of the immune system and to the suppressive effects of maternal antibodies. The activating receptor CD21 (CR2), when co-ligated with membrane IgM (mIgM) by complement-bound antigen lowers the threshold for activation of B lymphocytes. The inhibitory receptor CD32 (FcgammaRII) when co-ligated with mIgM by antigen-antibody complexes raises the threshold for activation. Expression of these receptors, which potentially play roles in regulation of B cell responses in the presence of maternal antibodies in neonates, has been recently characterized in blood lymphocytes in neonatal calves. Little is known however about expression of these receptors in the lymphoid tissues, where immune responses are initiated. In this study, expression of CD21, mIgM and CD32 receptors by B lymphocytes was studied in a range of lymphoid tissues including spleen, lymph nodes and bone marrow from newborn and 7-week-old calves using flow cytometry. The proportion of naïve B lymphocytes in the lymphocyte gate was significantly lower in blood and spleen of newborn calves compared to 7-week-old calves. Over 90% of B lymphocytes expressed CD21 in the lymphoid tissues. In the lymph nodes and spleen, a lower proportion of mIgM(+) B lymphocytes expressed CD32 compared to blood. In addition, intensity of expression of CD32 on B cells in lymph nodes was significantly lower compared to that in blood, suggesting a lower potential for inhibitory signalling in B cells in the lymphoid microenvironment. Investigation of the CD5(+) B cell population (as an indicator of B1 B cells) suggested an increase in the proportion of IgM(+)CD5(+) cells with age in calves, in both blood and lymphoid tissue, in contrast to the situation in humans and mice. Overall, the majority of naïve B lymphocytes in lymphoid tissues in neonatal calves expressed both activating (CD21, mIgM) and inhibitory (CD32) receptors. These

  15. The Innate Lymphoid Cell Precursor.

    PubMed

    Ishizuka, Isabel E; Constantinides, Michael G; Gudjonson, Herman; Bendelac, Albert

    2016-05-20

    The discovery of tissue-resident innate lymphoid cell populations effecting different forms of type 1, 2, and 3 immunity; tissue repair; and immune regulation has transformed our understanding of mucosal immunity and allergy. The emerging complexity of these populations along with compounding issues of redundancy and plasticity raise intriguing questions about their precise lineage relationship. Here we review advances in mapping the emergence of these lineages from early lymphoid precursors. We discuss the identification of a common innate lymphoid cell precursor characterized by transient expression of the transcription factor PLZF, and the lineage relationships of innate lymphoid cells with conventional natural killer cells and lymphoid tissue inducer cells. We also review the rapidly growing understanding of the network of transcription factors that direct the development of these lineages.

  16. Single nucleotide polymorphisms of mucosa-associated lymphoid tissue 1 in oral carcinoma cells and gingival fibroblasts.

    PubMed

    Oyama, Go; Midorikawa, Toshiaki; Matsumoto, Yasutaka; Takeyama, Mayu; Yamada, Kenji; Nozawa, Takaomi; Morikawa, Masako; Imai, Kazushi

    2013-07-01

    Oral carcinoma patients with inactivation of mucosa-associated lymphoid tissue 1 (MALT1) expression worsen their prognoses. Although the genetic mutation could be responsible for the inactivation, no information is available at present. In the present study, genomic DNA of oral carcinoma cells (HOC313, TSU, HSC2, HSC3, KOSC2, KOSC3, SCCKN, OSC19, Ca9.22, and Ho1u1 cells) and normal gingival fibroblasts (GF12 cells) derived from a Japanese population were amplified by polymerase chain reaction using primer sets spanning MALT1 exons, and nucleotide substitutions were analyzed by the single strand conformation polymorphism analysis. The substitutions were commonly observed in all cells, which express MALT1 at various levels. The substitutions at exons 1 and 9 were located at the 5' untranslated region and replaced (336)Asp to Asn, respectively, and others were positioned at the introns. Among the intronic substitutions, four were matched with the single nucleotide polymorphisms (SNPs) registered at the database. Since all cells were derived from a Japanese population, all substitutions detected are the SNPs. Absence of the carcinoma cell-specific mutation suggests that the inactivation of MALT1 expression but not the mutation promotes oral carcinoma progression.

  17. Interleukin-1β selectively expands and sustains interleukin-22+ immature human natural killer cells in secondary lymphoid tissue

    PubMed Central

    Hughes, Tiffany; Becknell, Brian; Freud, Aharon G.; McClory, Susan; Briercheck, Edward; Yu, Jianhua; Mao, Charlene; Giovenzana, Chiara; Nuovo, Gerard; Wei, Lai; Zhang, Xiaoli; Gavrilin, Mikhail A.; Wewers, Mark D.; Caligiuri, Michael A.

    2013-01-01

    SUMMARY Among human natural killer (NK) cell intermediates in secondary lymphoid tissue (SLT), stage 3 CD34− CD117+CD161+CD94− immature NK (iNK) cells uniquely express aryl hydrocarbon receptor (AHR) and interleukin-22 (IL-22), supporting a role in mucosal immunity. The mechanisms controlling proliferation and differentiation of these cells are unknown. Here we demonstrate that the IL-1 receptor IL-1R1 was selectively expressed by a subpopulation of iNK cells that localized proximal to IL-1β-producing conventional dendritic cells (cDCs) within SLT. IL-1R1hi iNK cells required continuous exposure to IL-1β to retain AHR and IL-22 expression, and proliferate in direct response to cDC-derived IL-15 and IL-1β. In the absence of IL-1β, a substantially greater fraction of IL-1R1hi iNK cells differentiated to stage 4 NK cells and acquired the ability to kill and secrete IFN-γ. Thus, cDC-derived IL-1β preserves and expands IL-1R1hiIL-22+AHR+ iNK cells, potentially influencing human mucosal innate immunity during infection. PMID:20620944

  18. Persistence of pulmonary tertiary lymphoid tissues and anti-nuclear antibodies following cessation of cigarette smoke exposure.

    PubMed

    Morissette, Mathieu C; Jobse, Brian N; Thayaparan, Danya; Nikota, Jake K; Shen, Pamela; Labiris, Nancy Renée; Kolbeck, Roland; Nair, Parameswaran; Humbles, Alison A; Stämpfli, Martin R

    2014-04-22

    Formation of pulmonary tertiary immune structures is a characteristic feature of advanced COPD. In the current study, we investigated the mechanisms of tertiary lymphoid tissue (TLT) formation in the lungs of cigarette smoke-exposed mice. We found that cigarette smoke exposure led to TLT formation that persisted following smoking cessation. TLTs consisted predominantly of IgM positive B cells, while plasma cells in close proximity to TLTs expressed IgM, IgG, and IgA. The presence of TLT formation was associated with anti-nuclear autoantibody (ANA) production that also persisted following smoking cessation. ANAs were observed in the lungs, but not the circulation of cigarette smoke-exposed mice. Similarly, we observed ANA in the sputum of COPD patients where levels correlated with disease severity and were refractory to steroid treatment. Both ANA production and TLT formation were dependent on interleukin-1 receptor 1 (IL-1R1) expression. Contrary to TLT and ANA, lung neutrophilia resolved following smoking cessation. These data suggest a differential regulation of innate and B cell-related immune inflammatory processes associated with cigarette smoke exposure. Moreover, our study further emphasizes the importance of interleukin-1 (IL-1) signaling pathways in cigarette smoke-related pulmonary pathogenesis.

  19. Primary mucosa-associated lymphoid tissue lymphoma of the liver: A report of two cases and review of the literature

    PubMed Central

    Obiorah, Ifeyinwa E; Johnson, Lynt; Ozdemirli, Metin

    2017-01-01

    Mucosa-associated lymphoid tissue (MALT) lymphoma of the liver is a very rare condition and thus the diagnosis may be challenging. The clinical presentation is usually variable, ranging from minimal clinical symptoms to severe end stage liver disease. In this paper, we describe the clinicopathologic findings in two cases of primary hepatic MALT lymphoma. One case is an 80-year-old female with no underlying chronic liver disease and the second case is a 30-year-old female with autoimmune hepatitis complicated by MALT lymphoma. In both specimens, there was diffuse infiltration of atypical B-lymphocytes that were positive for CD20 and CD79a, but negative for CD5, CD43 and CD10. There were occasional lymphoepithelial lesions involving the hepatocytes or bile ducts. Polymerase chain reaction analysis showed monoclonal immunoglobulin heavy chain gene rearrangement in both cases. The first case was treated with surgery but developed pulmonary recurrence a year after complete resection but went into remission following treatment with rituximab. A second recurrence occurred in the right parotid gland 7 years later, which was treated with idelalisib. The second case was effectively treated with rituximab. To our knowledge, the second case is the first reported case linked to autoimmune hepatitis. PMID:28217252

  20. T cell-dependent antitumor immunity mediated by secondary lymphoid tissue chemokine: augmentation of dendritic cell-based immunotherapy.

    PubMed

    Kirk, C J; Hartigan-O'Connor, D; Nickoloff, B J; Chamberlain, J S; Giedlin, M; Aukerman, L; Mule, J J

    2001-03-01

    Secondary lymphoid tissue chemokine (SLC) is a CC chemokine that is selective in its recruitment of naive T cells and dendritic cells (DCs). In the lymph node, SLC is believed to play an important role in the initiation of an immune response by colocalizing naive T cells with DC-presenting antigen. Here, we used SLC as a treatment for tumors established from the poorly immunogenic B16 melanoma. Intratumoral injections of SLC inhibited tumor growth in a CD8+, T cell-dependent manner. SLC elicited a substantial infiltration of DCs and T cells into the tumor, coincident with the antitumor response. We next used SLC gene-modified DCs as a treatment of established tumors. Intratumoral injections of SLC-expressing DCs resulted in tumor growth inhibition that was significantly better than either control DCs or SLC alone. Distal site immunization of tumor-bearing mice with SLC gene-modified DCs pulsed with tumor lysate elicited an antitumor response whereas control DCs did not. We also found that s.c. injection of lysate-pulsed DCs expressing SLC promoted the migration of T cells to the immunization site. This report demonstrates that SLC can both induce antitumor responses and enhance the antitumor immunity elicited by DCs.

  1. Trisomy 3 is not a common feature in malignant lymphomas of mucosa-associated lymphoid tissue type.

    PubMed

    Ott, G; Kalla, J; Steinhoff, A; Rosenwald, A; Katzenberger, T; Roblick, U; Ott, M M; Müller-Hermelink, H K

    1998-09-01

    The genetic background of extranodal marginal zone B-cell non-Hodgkin's lymphoma (NHL) of mucosa-associated lymphoid tissue (MALT) type is poorly understood. In contrast to most entities of primary nodal lymphomas, few cytogenetic data are available, and gene rearrangements frequently encountered in and highly characteristic of certain entities of systemic NHL are absent in this type of lymphoma. Recently, it was suggested that MALT-type NHLs are associated with certain numerical chromosome aberrations and especially with trisomy 3. We performed an extensive study using a sensitive double (bicolor) fluorescence in situ hybridization technique for the analysis of trisomies for chromosomes 3, 7, 12, and 18 in 60 samples of low-grade and 45 high-grade MALT-type tumors. In the low-grade cases, trisomy 3 was found in a frequency of only 20%. High-grade lymphomas of MALT type were associated with trisomies 3, 7, 12, and 18 in 36, 20, 18, and 13% of the cases, respectively. Whereas no difference was encountered for trisomy 3 in primary and secondary/simultaneous high-grade lymphomas, +7 and +12 were associated with primary lymphomas, and a +18 was predominantly found in secondary/simultaneous high-grade NHL. These results challenge earlier reports describing a high frequency of +3 in low-grade MALT-type NHL and indicate a possibly different genetic evolution pattern of primary and secondary/simultaneous high-grade lymphomas of primary mucosal origin.

  2. Mucosa-associated lymphoid tissue (MALT) variant of primary rectal lymphoma: a review of the English literature.

    PubMed

    Kelley, Scott R

    2017-03-01

    Primary rectal lymphoma (PRL) is the third most common cause of rectal cancer following adenocarcinoma (90-95 %) and carcinoid (5 %). The most common variant of PRL is the mucosa-associated lymphoid tissue (MALT) type. To date, no study has been able to recommend an optimal treatment algorithm for this rare disease. The aim of our study was to review the English literature on primary rectal MALT lymphoma. A review of the English literature was conducted to identify articles describing the MALT variant of PRL. Fifty-one cases were identified. A complete response was achieved in 12 of 19 cases treated with Helicobacter pylori eradication therapy, 5 of 6 with radiation, 2 of 4 cases with chemotherapy, 2 of 4 with endoscopic resection, 6 of 8 cases with surgical resection, and all 8 with combination therapies. Cases failing initial therapies were responsive to various second-line treatments. Two cases spontaneously regressed with observation alone. Complete regression of primary rectal MALT lymphoma was achieved using various therapeutic strategies, although the numbers of different treatment modalities are too small to draw definitive conclusions.

  3. Differential infection patterns of CD4+ T cells and lymphoid tissue viral burden distinguish progressive and nonprogressive lentiviral infections

    PubMed Central

    Vinton, Carol; Tabb, Brian; Hao, Xing Pei; Connick, Elizabeth; Paiardini, Mirko; Lifson, Jeffrey D.; Silvestri, Guido

    2012-01-01

    Nonhuman primate natural hosts for simian immunodeficiency viruses (SIV) develop a nonresolving chronic infection but do not develop AIDS. Mechanisms to explain the nonprogressive nature of SIV infection in natural hosts that underlie maintained high levels of plasma viremia without apparent loss of target cells remain unclear. Here we used comprehensive approaches (ie, FACS sorting, quantitative RT-PCR, immunohistochemistry, and in situ hybridization) to study viral infection within subsets of peripheral blood and lymphoid tissue (LT) CD4+ T cells in cohorts of chronically SIV-infected rhesus macaques (RMs), HIV-infected humans, and SIVsmm-infected sooty mangabeys (SMs). We find: (1) infection frequencies among CD4+ T cells in chronically SIV-infected RMs are significantly higher than those in SIVsmm-infected SMs; (2) infected cells are found in distinct anatomic LT niches and different CD4+ T-cell subsets in SIV-infected RMs and SMs, with infection patterns of RMs reflecting HIV infection in humans; (3) TFH cells are infected at higher frequencies in RMs and humans than in SMs; and (4) LT viral burden, including follicular dendritic cell deposition of virus, is increased in RMs and humans compared with SMs. These data provide insights into how natural hosts are able to maintain high levels of plasma viremia while avoiding development of immunodeficiency. PMID:22990012

  4. Noninfectious X4 but not R5 human immunodeficiency virus type 1 virions inhibit humoral immune responses in human lymphoid tissue ex vivo

    NASA Technical Reports Server (NTRS)

    Fitzgerald, Wendy; Sylwester, Andrew W.; Grivel, Jean-Charles; Lifson, Jeffrey D.; Margolis, Leonid B.

    2004-01-01

    Ex vivo human immunodeficiency virus type 1 (HIV-1) infection of human lymphoid tissue recapitulates some aspects of in vivo HIV-1 infection, including a severe depletion of CD4(+) T cells and suppression of humoral immune responses to recall antigens or to polyclonal stimuli. These effects are induced by infection with X4 HIV-1 variants, whereas infection with R5 variants results in only mild depletion of CD4(+) T cells and no suppression of immune responses. To study the mechanisms of suppression of immune responses in this ex vivo system, we used aldrithiol-2 (AT-2)-inactivated virions that have functional envelope glycoproteins but are not infectious and do not deplete CD4(+) T cells in human lymphoid tissues ex vivo. Nevertheless, AT-2-inactivated X4 (but not R5) HIV-1 virions, even with only a brief exposure, inhibit antibody responses in human lymphoid tissue ex vivo, similarly to infectious virus. This phenomenon is mediated by soluble immunosuppressive factor(s) secreted by tissue exposed to virus.

  5. Epithelial control of gut-associated lymphoid tissue formation through p38α-dependent restraint of NF-κB signaling

    PubMed Central

    Caballero-Franco, Celia; Guma, Monica; Choo, Min-Kyung; Sano, Yasuyo; Enzler, Thomas; Karin, Michael; Mizoguchi, Atsushi; Park, Jin Mo

    2015-01-01

    The protein kinase p38α mediates cellular responses to environmental and endogenous cues that direct tissue homeostasis and immune responses. Studies of mice lacking p38α in several different cell types have demonstrated that p38α signaling is essential to maintaining the proliferation-differentiation balance in developing and steady-state tissues. The mechanisms underlying these roles involve cell-autonomous control of signaling and gene expression by p38α. Here we show that p38α regulates gut-associated lymphoid tissue (GALT) formation in a non-cell-autonomous manner. From an investigation of mice with intestinal epithelial cell-specific deletion of the p38α gene, we find that p38α serves to limit NF-κB signaling and thereby attenuate GALT-promoting chemokine expression in the intestinal epithelium. Loss of this regulation results in GALT hyperplasia and, in some animals, mucosa-associated B cell lymphoma. These anomalies occur independently of luminal microbial stimuli and are likely driven by direct epithelial-lymphoid interactions. Our study illustrates a novel p38α-dependent mechanism preventing excessive generation of epithelial-derived signals that drive lymphoid tissue overgrowth and malignancy. PMID:26792803

  6. Noninfectious X4 but not R5 human immunodeficiency virus type 1 virions inhibit humoral immune responses in human lymphoid tissue ex vivo

    NASA Technical Reports Server (NTRS)

    Fitzgerald, Wendy; Sylwester, Andrew W.; Grivel, Jean-Charles; Lifson, Jeffrey D.; Margolis, Leonid B.

    2004-01-01

    Ex vivo human immunodeficiency virus type 1 (HIV-1) infection of human lymphoid tissue recapitulates some aspects of in vivo HIV-1 infection, including a severe depletion of CD4(+) T cells and suppression of humoral immune responses to recall antigens or to polyclonal stimuli. These effects are induced by infection with X4 HIV-1 variants, whereas infection with R5 variants results in only mild depletion of CD4(+) T cells and no suppression of immune responses. To study the mechanisms of suppression of immune responses in this ex vivo system, we used aldrithiol-2 (AT-2)-inactivated virions that have functional envelope glycoproteins but are not infectious and do not deplete CD4(+) T cells in human lymphoid tissues ex vivo. Nevertheless, AT-2-inactivated X4 (but not R5) HIV-1 virions, even with only a brief exposure, inhibit antibody responses in human lymphoid tissue ex vivo, similarly to infectious virus. This phenomenon is mediated by soluble immunosuppressive factor(s) secreted by tissue exposed to virus.

  7. Epithelial Control of Gut-Associated Lymphoid Tissue Formation through p38α-Dependent Restraint of NF-κB Signaling.

    PubMed

    Caballero-Franco, Celia; Guma, Monica; Choo, Min-Kyung; Sano, Yasuyo; Enzler, Thomas; Karin, Michael; Mizoguchi, Atsushi; Park, Jin Mo

    2016-03-01

    The protein kinase p38α mediates cellular responses to environmental and endogenous cues that direct tissue homeostasis and immune responses. Studies of mice lacking p38α in several different cell types have demonstrated that p38α signaling is essential to maintaining the proliferation-differentiation balance in developing and steady-state tissues. The mechanisms underlying these roles involve cell-autonomous control of signaling and gene expression by p38α. In this study, we show that p38α regulates gut-associated lymphoid tissue (GALT) formation in a noncell-autonomous manner. From an investigation of mice with intestinal epithelial cell-specific deletion of the p38α gene, we find that p38α serves to limit NF-κB signaling and thereby attenuate GALT-promoting chemokine expression in the intestinal epithelium. Loss of this regulation results in GALT hyperplasia and, in some animals, mucosa-associated B cell lymphoma. These anomalies occur independently of luminal microbial stimuli and are most likely driven by direct epithelial-lymphoid interactions. Our study illustrates a novel p38α-dependent mechanism preventing excessive generation of epithelial-derived signals that drive lymphoid tissue overgrowth and malignancy.

  8. [PECULIARITIES OF THE CELLULAR COMPOSITION OF SPLENIC LYMPHOID TISSUE IN MICE AFTER LONG-TERM USE OF LIGHT WATER AND IRRADIATION].

    PubMed

    Grigorenko, D Ye

    2015-01-01

    The changes of the cellular composition of splenic lymphoid tissue were studied 7, 15 and 30 days after irradiation with a dose of 50 rad, in BALB/c mice which received either distilled water or light (deuterium-depleted) water for a long time prior to and after irradiation. The irregular pattern of changes of splenic cellular composition was observed during the experiment. It was found that at day 7 after irradiation, the splenic structural zones in mice demonstrated a sharp decrease in the number of blast forms and mitotic cells, reflecting a lower level of lymphocytopoiesis, as well as an increased cellular destruction in mice consuming light water. By day 30 of the experiment, different responses of lymphoid structures were observed in the organ. In the periarteriolar lymphoid sheaths, the processes of cellular composition regeneration were more pronounced than in the germinal centers of lymphoid nodules, indicating the enhancement of body cell-mediated immunity and immunomodulating properties of light water in mice at later dates of post-irradiation period.

  9. [Cellular composition of diffuse lymphoid tissue in the mucous membrane of human larynx under conditions of physiological norm and in fatal hypothermia in the Republic of Sakha (Yakutia)].

    PubMed

    Buzinaeva, M T; Garmayeva, D K

    2013-01-01

    Using histological, morphometric and immunnohistochemical methods, cellular composition and cytoarchitectonics of diffuse lymphoid tissue in the mucous membrane of the larynx was studied in 29 men aged 17-74 years, who died from general body hypothermia in the winter period and in 27 men who died from mechanical injury during the summer. Significant changes in the cellular composition of diffuse lymphoid tissue of the mucous membrane in the various parts of the larynx were detected in fatal hypothermia, which included the decrease in the number of T-, B-lymphocytes and plasma cells and the increase in the number of macrophages in all age groups, indicating the suppression of local immunity in persons who died due to the action of low temperature.

  10. Immunoreactivity for IL-1 beta and TNF alpha in human lymphoid and nonlymphoid tissues.

    PubMed Central

    Ruco, L. P.; Stoppacciaro, A.; Pomponi, D.; Boraschi, D.; Santoni, A.; Tagliabue, A.; Uccini, S.; Baroni, C. D.

    1989-01-01

    Monoclonal antibodies (MAbs) against two non-cross-reacting antigens of human IL-1 beta (Vhp20 and BRhC3) and human TNF alpha (B154.2 and B154.7) were applied to identify cytokine-containing cells in tissue sections and in cell suspensions. IL-1 beta- or TNF alpha-positive cells were not present in immunostained cytocentrifuge smears prepared from freshly isolated peripheral blood leukocytes, spleen, and lymph node cells. After 18 hours of culture with bacterial endotoxin (LPS), 80% to 90% of blood monocytes, 30% of spleen macrophages, and 2% to 28% of lymph node macrophages were strongly positive for IL-1 beta with either of the MAbs. Furthermore, 25% to 35% of blood monocytes and 6% to 60% of lymph node macrophages were stained for TNF alpha. Cells positive for IL-1 beta or TNF alpha were extremely rare in sections of normal thymus, spleen, and lymph nodes. Immunoreactivity for IL-1 beta or TNF alpha was frequently observed in sections of granulomatous lymphadenitis (N = 11). IL-1 beta or TNF alpha staining was confined to the epithelioid macrophages forming the granuloma, and the intensity of TNF alpha reactivity was generally stronger. The high frequency of cytokine-containing cells in this pathologic condition was confirmed in a cell suspension study showing that 20% of epithelioid macrophages were weakly positive for IL-1 beta and 80% were strongly positive for TNF alpha. The presence of cytokine-containing cells was investigated in cryostat sections of several nonlymphoid organs with normal histologic appearance. IL-1 beta reactivity was not observed in any of the tissues. TNF alpha reactivity was frequently demonstrated in isolated macrophages embedded in the interstitial connective tissue. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:2683798

  11. Distribution of a macaque immunosuppressive type D retrovirus in neural, lymphoid, and salivary tissues

    SciTech Connect

    Lackner, A.A.; Rodriguez, M.H.; Bush, C.E.; Munn, R.J.; Kwang, Hweising; Moore, P.F.; Osborn, K.G.; Marx, P.A.; Gardner, M.B.; Lowenstine, L.J. )

    1988-06-01

    Simian acquired immune deficiency syndrome (SAIDS) in rhesus macaques (Macaca mulatta) at the California Primate Research Center is caused by a type D retrovirus designated SAIDS retrovirus serotype 1 (SRV-1). This syndrome is characterized by profound immunosuppression and death associated with opportunistic infections. Neurologic signs and lesions have not been described as part of this syndrome. The distribution of SRV-1 in the salivary glands, lymph nodes, spleens, thymuses, and brains of eight virus-infected rhesus macaques was examined by immunohistochemistry. Electron microscopy, in situ RNA hybridization, and Southern blot hybridization were also performed on selected tissues to detect viral particles, RNA, and DNA, respectively. In seven of eight SRV-1-infected animals, the transmembrane envelope glycoprotein (gp20) of SRV-1 was present in three or more tissues, but never in the brain. In the remaining animal, no viral antigen was detected in any tissue. In this same group of animals, viral nucleic acid was detected in the lymph nodes of six of six animals by Southern blot hybridization, in the salivary glands of two of five animals by both Southern blot and in situ hybridizations, and, surprisingly, in the brains of three of three animals by Southern blot and of three of five animals by in situ hybridization, including the one animal in which viral gp20 was undetectable. None of these animals had neurologic signs or lesions. The detection of viral nucleic acid in the absence of viral antigen in the brain suggests latent SRV-1 infection of the central nervous system.

  12. Compartmentalization of Total and Virus-Specific Tissue-Resident Memory CD8+ T Cells in Human Lymphoid Organs.

    PubMed

    Woon, Heng Giap; Braun, Asolina; Li, Jane; Smith, Corey; Edwards, Jarem; Sierro, Frederic; Feng, Carl G; Khanna, Rajiv; Elliot, Michael; Bell, Andrew; Hislop, Andrew D; Tangye, Stuart G; Rickinson, Alan B; Gebhardt, Thomas; Britton, Warwick J; Palendira, Umaimainthan

    2016-08-01

    Disruption of T cell memory during severe immune suppression results in reactivation of chronic viral infections, such as Epstein Barr virus (EBV) and Cytomegalovirus (CMV). How different subsets of memory T cells contribute to the protective immunity against these viruses remains poorly defined. In this study we examined the compartmentalization of virus-specific, tissue resident memory CD8+ T cells in human lymphoid organs. This revealed two distinct populations of memory CD8+ T cells, that were CD69+CD103+ and CD69+CD103-, and were retained within the spleen and tonsils in the absence of recent T cell stimulation. These two types of memory cells were distinct not only in their phenotype and transcriptional profile, but also in their anatomical localization within tonsils and spleen. The EBV-specific, but not CMV-specific, CD8+ memory T cells preferentially accumulated in the tonsils and acquired a phenotype that ensured their retention at the epithelial sites where EBV replicates. In vitro studies revealed that the cytokine IL-15 can potentiate the retention of circulating effector memory CD8+ T cells by down-regulating the expression of sphingosine-1-phosphate receptor, required for T cell exit from tissues, and its transcriptional activator, Kruppel-like factor 2 (KLF2). Within the tonsils the expression of IL-15 was detected in regions where CD8+ T cells localized, further supporting a role for this cytokine in T cell retention. Together this study provides evidence for the compartmentalization of distinct types of resident memory T cells that could contribute to the long-term protection against persisting viral infections.

  13. Orbital and ocular adnexal Mucosa-Associated Lymphoid Tissue (MALT) lymphomas: a single-center 10-year experience.

    PubMed

    Smiljanic, M; Milosevic, R; Antic, D; Andjelic, B; Djurasinovic, V; Todorovic, M; Bila, J; Bogdanovic, A; Mihaljevic, B

    2013-12-01

    Orbital and ocular andexal Mucosa-Associated Lymphoid Tissue Lymphoma (MALT) or ocular adnexal MALT lymphoma (OAML) is the most common of all eye non-Hodgkin lymphomas. Autoimmune inflammatory disorders and chronic infections are important etiological factors and CD5 and CD43 (sialophorin) tumor markers are significant negative prognostic factors. Disease signs and symptoms can occur a long time before diagnosis. Varieties of treatment options are available. The aim of this retrospective analysis was to compare the efficiency of different treatment options and to investigate disease outcome. Twenty OAML patients, diagnosed in the Clinic of Hematology, Clinical Centre of Serbia, between 2003 and 2013, were enrolled. In most cases, OAML developed in the eighth decade with greater incidence in the male population. Median age was 67.5 years. The median period between the appearance of local signs and symptoms and diagnosis was 7 months. The dominant sign at presentation was swelling of involved tissue (40%). The most common was orbital involvement (55%). All patients had localized disease. Observed laboratory parameters on presentation showed low disease activity. Sialophorin prognostic significance was not registered. Our patients were initially treated differently but there was no significant difference in progression-free survival (PFS) due to initial treatment option (p = 0.2957). Median PFS was 22 months (3-89), and 5-year PFS was 60%. Median overall survival (OS) was 43 months (1-105) and 5-year OS 95%. Eight patients (40%) relapsed and one patient died due to non-hematological complications. In our experience, most modern induction treatment options appear to result in the same, favorable outcome.

  14. Compartmentalization of Total and Virus-Specific Tissue-Resident Memory CD8+ T Cells in Human Lymphoid Organs

    PubMed Central

    Li, Jane; Smith, Corey; Edwards, Jarem; Sierro, Frederic; Feng, Carl G.; Khanna, Rajiv; Bell, Andrew; Hislop, Andrew D.; Tangye, Stuart G.; Rickinson, Alan B.; Gebhardt, Thomas; Britton, Warwick J.

    2016-01-01

    Disruption of T cell memory during severe immune suppression results in reactivation of chronic viral infections, such as Epstein Barr virus (EBV) and Cytomegalovirus (CMV). How different subsets of memory T cells contribute to the protective immunity against these viruses remains poorly defined. In this study we examined the compartmentalization of virus-specific, tissue resident memory CD8+ T cells in human lymphoid organs. This revealed two distinct populations of memory CD8+ T cells, that were CD69+CD103+ and CD69+CD103—, and were retained within the spleen and tonsils in the absence of recent T cell stimulation. These two types of memory cells were distinct not only in their phenotype and transcriptional profile, but also in their anatomical localization within tonsils and spleen. The EBV-specific, but not CMV-specific, CD8+ memory T cells preferentially accumulated in the tonsils and acquired a phenotype that ensured their retention at the epithelial sites where EBV replicates. In vitro studies revealed that the cytokine IL-15 can potentiate the retention of circulating effector memory CD8+ T cells by down-regulating the expression of sphingosine-1-phosphate receptor, required for T cell exit from tissues, and its transcriptional activator, Kruppel-like factor 2 (KLF2). Within the tonsils the expression of IL-15 was detected in regions where CD8+ T cells localized, further supporting a role for this cytokine in T cell retention. Together this study provides evidence for the compartmentalization of distinct types of resident memory T cells that could contribute to the long-term protection against persisting viral infections. PMID:27540722

  15. Six-colour fluorescent imaging of lymphoid tissue based on colour addition theory.

    PubMed

    Ma, Bin; Winkelbach, Simon; Lindenmaier, Werner; Dittmar, Kurt E J

    2006-01-01

    Multi-colour imaging of immunofluorescently labelled tissue using confocal microscopy was accomplished by using colour addition theory. This new technique includes several improvements for immunolabelling: (1) the co-localization of two or more markers on one cell for the identification of specific cell populations; (2) the co-localization of two fluorescent dyes from secondary reagents for the identification of the cells; (3) a multi-step staining protocol with two primary antibodies originating from the same host species or with two or three biotin-conjugated primary antibodies. After image acquisition, colour segmentation/unmixing are applied to the single multi-colour image to generate multi-pseudo-channels for individual or co-localized fluorescent dyes. With this new technique, we have been able to visualize six cell populations simultaneously in the mouse lymph node and intestine. The efficiency of this method has also been demonstrated in the three-dimensional reconstruction of thick sections from mouse ileum. Our method is simple, efficient, and may be indispensable in experimental cell and tissue studies requiring multiple immunolabelling.

  16. Mucosa-Associated Lymphoid Tissue Lymphoma of the Sigmoid Colon Discovered on Routine Screening Colonoscopy in Patient with Hepatitis C and Helicobacter pylori Infection.

    PubMed

    Bhuta, Rajiv; Bromberg, Michael; Bains, Ashish; Schey, Ron

    2016-08-01

    Mucosa-associated lymphoid tissue (MALT) lymphoma is predominantly found in the stomach. Rarely, it is found in the proximal colon and even less so in the sigmoid colon. We present a rare case of primary sigmoid colon MALT lymphoma in a patient with concomitant Helicobacter pylori and hepatitis C infection. We also review current imaging, staging, and therapeutic modalities. To our knowledge, this is the first sigmoid colon MALT lymphoma reported in the United States.

  17. Primary Marginal Zone B-Cell Lymphoma of the Mucosa-Associated Lymphoid Tissue of the Lacrimal Sac Found with Epiphora: A Case Report

    PubMed Central

    Kitaguchi, Yoshiyuki; Takahashi, Yasuhiro; Mupas-Uy, Jacqueline; Takahashi, Emiko; Kakizaki, Hirohiko

    2016-01-01

    We report a case of a primary marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue of the lacrimal sac, which was found in a patient with epiphora without palpable mass. Magnetic resonance imaging demonstrated mucosal thickening of the lacrimal sac with a patent lumen, consistent with the intraoperative finding. Epiphora resolved, which was confirmed by smooth syringing, 1 month after starting the immunotherapy. PMID:27790131

  18. Mucosa-Associated Lymphoid Tissue Lymphoma of the Sigmoid Colon Discovered on Routine Screening Colonoscopy in Patient with Hepatitis C and Helicobacter pylori Infection

    PubMed Central

    Bhuta, Rajiv; Bromberg, Michael; Bains, Ashish

    2016-01-01

    Mucosa-associated lymphoid tissue (MALT) lymphoma is predominantly found in the stomach. Rarely, it is found in the proximal colon and even less so in the sigmoid colon. We present a rare case of primary sigmoid colon MALT lymphoma in a patient with concomitant Helicobacter pylori and hepatitis C infection. We also review current imaging, staging, and therapeutic modalities. To our knowledge, this is the first sigmoid colon MALT lymphoma reported in the United States. PMID:27807552

  19. Identification of dendritic cells, B cell and T cell subsets in Tasmanian devil lymphoid tissue; evidence for poor immune cell infiltration into devil facial tumors.

    PubMed

    Howson, Lauren J; Morris, Katrina M; Kobayashi, Takumi; Tovar, Cesar; Kreiss, Alexandre; Papenfuss, Anthony T; Corcoran, Lynn; Belov, Katherine; Woods, Gregory M

    2014-05-01

    The Tasmanian devil is under threat of extinction due to the transmissible devil facial tumor disease (DFTD). This fatal tumor is an allograft that does not induce an immune response, raising questions about the activity of Tasmanian devil immune cells. T and B cell analysis has been limited by a lack of antibodies, hence the need to produce such reagents. Amino acid sequence analysis revealed that CD4, CD8, IgM, and IgG were closely related to other marsupials. Monoclonal antibodies were produced against CD4, CD8, IgM, and IgG by generating bacterial fusion proteins. These, and commercial antibodies against CD1a and CD83, identified T cells, B cells and dendritic cells by immunohistochemistry. CD4(+) and CD8(+) T cells were identified in pouch young thymus, adult lymph nodes, spleen, bronchus- and gut-associated lymphoid tissue. Their anatomical distribution was characteristic of mammalian lymphoid tissues with more CD4(+) than CD8(+) cells in lymph nodes and splenic white pulp. IgM(+) and IgG(+) B cells were identified in adult lymph nodes, spleen, bronchus-associated lymphoid tissue and gut-associated lymphoid tissue, with more IgM(+) than IgG(+) cells. Dendritic cells were identified in lymph node, spleen and skin. This distribution is consistent with eutherian mammals and other marsupials, indicating they have the immune cell subsets for an anti-tumor immunity. Devil facial tumor disease tumors contained more CD8(+) than CD4(+) cells, but in low numbers. There were also low numbers of CD1a(+) and MHC class II(+) cells, but no CD83(+) IgM(+) or IgG(+) B cells, consistent with poor immune cell infiltration. © 2014 The Authors. The Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology Published by Wiley Periodicals, Inc.

  20. Reduced Inflammation and Lymphoid Tissue Immunopathology in Rhesus Macaques Receiving Anti–Tumor Necrosis Factor Treatment During Primary Simian Immunodeficiency Virus Infection

    PubMed Central

    Tabb, Brian; Morcock, David R.; Trubey, Charles M.; Quiñones, Octavio A.; Hao, Xing Pei; Smedley, Jeremy; Macallister, Rhonda; Piatak, Michael; Harris, Levelle D.; Paiardini, Mirko; Silvestri, Guido; Brenchley, Jason M.; Alvord, W. Gregory; Lifson, Jeffrey D.; Estes, Jacob D.

    2013-01-01

    Background. Human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infections induce robust, generalized inflammatory responses that begin during acute infection and lead to pathological systemic immune activation, fibrotic damage of lymphoid tissues, and CD4+ T-cell loss, pathogenic processes that contribute to disease progression. Methods. To better understand the contribution of tumor necrosis factor (TNF), a key regulator of acute inflammation, to lentiviral pathogenesis, rhesus macaques newly infected with SIVmac239 were treated for 12 weeks in a pilot study with adalimumab (Humira), a human anti-TNF monoclonal antibody. Results. Adalimumab did not affect plasma SIV RNA levels or measures of T-cell immune activation (CD38 or Ki67) in peripheral blood or lymph node T cells. However, compared with untreated rhesus macaques, adalimumab-treated rhesus macaques showed attenuated expression of proinflammatory genes, decreased infiltration of polymorphonuclear cells into the T-cell zone of lymphoid tissues, and weaker antiinflammatory regulatory responses to SIV infection (ie, fewer presumed alternatively activated [ie, CD163+] macrophages, interleukin 10–producing cells, and transforming growth factor β–producing cells), along with reduced lymphoid tissue fibrosis and better preservation of CD4+ T cells. Conclusions. While HIV/SIV replication drives pathogenesis, these data emphasize the contribution of the inflammatory response to lentiviral infection to overall pathogenesis, and they suggest that early modulation of the inflammatory response may help attenuate disease progression. PMID:23087435

  1. Abortive HIV Infection Mediates CD4 T-Cell Depletion and Inflammation in Human Lymphoid Tissue

    PubMed Central

    Doitsh, Gilad; Cavrois, Marielle; Lassen, Kara G.; Zepeda, Orlando; Yang, Zhiyuan; Santiago, Mario L.; Hebbeler, Andrew M.; Greene, Warner C.

    2010-01-01

    Summary The mechanism by which CD4 T-cells are depleted in HIV-infected hosts remains poorly understood. In ex vivo cultures of human tonsil tissue, CD4 T cells undergo a pronounced cytopathic response following HIV infection. Strikingly, >95% of these dying cells are not productively infected but instead correspond to bystander cells. We now show that the death of these “bystander” cells involves abortive HIV infection. Inhibitors blocking HIV entry or early steps of reverse transcription prevent CD4 T-cell death while inhibition of later events in viral life cycle does not. We propose that the nonpermissive state exhibited by the majority of resting CD4 tonsil T-cells leads to accumulation of incomplete reverse transcripts. These cytoplasmic nucleic acids activate a host defense program that elicits a coordinated proapoptotic and proinflammatory response involving caspase-3 and caspase-1 activation. While this response likely evolved to protect the host, it centrally contributes to the immunopathogenic effects of HIV. PMID:21111238

  2. Abortive HIV infection mediates CD4 T cell depletion and inflammation in human lymphoid tissue.

    PubMed

    Doitsh, Gilad; Cavrois, Marielle; Lassen, Kara G; Zepeda, Orlando; Yang, Zhiyuan; Santiago, Mario L; Hebbeler, Andrew M; Greene, Warner C

    2010-11-24

    The mechanism by which CD4 T cells are depleted in HIV-infected hosts remains poorly understood. In ex vivo cultures of human tonsil tissue, CD4 T cells undergo a pronounced cytopathic response following HIV infection. Strikingly, >95% of these dying cells are not productively infected but instead correspond to bystander cells. We now show that the death of these "bystander" cells involves abortive HIV infection. Inhibitors blocking HIV entry or early steps of reverse transcription prevent CD4 T cell death while inhibition of later events in the viral life cycle does not. We demonstrate that the nonpermissive state exhibited by the majority of resting CD4 tonsil T cells leads to accumulation of incomplete reverse transcripts. These cytoplasmic nucleic acids activate a host defense program that elicits a coordinated proapoptotic and proinflammatory response involving caspase-3 and caspase-1 activation. While this response likely evolved to protect the host, it centrally contributes to the immunopathogenic effects of HIV. Copyright © 2010 Elsevier Inc. All rights reserved.

  3. Aging Impairs Murine B Cell Differentiation and Function in Primary and Secondary Lymphoid Tissues

    PubMed Central

    Frasca, Daniela; Blomberg, Bonnie B

    2011-01-01

    Age-related changes in humoral immunity are responsible for the reduced vaccine responses observed in elderly individuals. Although aging has been shown to affect T cells, dendritic cells and macrophages and these effects significantly impact humoral responses, intrinsic alterations in B cells also occur. We here provide an overview of age-related changes in mouse B cells. In particular, we summarize data from the literature showing age-related changes in B cell differentiation in the bone marrow, in B cell marker expression and cell survival in the periphery and in the ability to make specific antibodies in both splenic and mucosal tissues. Moreover, we summarize the results from our studies showing that the ability to undergo class switch recombination, the enzyme activation-induced cytidine deaminase and the transcription factor E47 are all decreased in stimulated B cells from old mice. The defects presented in this review for aged B cells should allow the discovery of strategies for improvement of humoral immune responses in both humans and mice in the near future. PMID:22396888

  4. Atypical Epstein-Barr viral genomic structure in lymphoma tissue and lymphoid cell lines.

    PubMed

    Tang, Weihua; Fan, Hongxin; Schroeder, Jane; Dunphy, Cherie H; Bryant, Ronald J; Fedoriw, Yuri; Gulley, Margaret L

    2013-06-01

    Epstein-Barr virus (EBV) DNA is found within the malignant cells of some subtypes of lymphoma, and viral presence is being exploited for improved diagnosis, monitoring, and management of affected patients. Recent work suggests that viral genomic polymorphism, such as partial deletion of the viral genome, could interfere with virus detection in tumor tissues. To test for atypical forms of the EBV genome, 98 lymphomas and 6 infected cell lines were studied using a battery of 6 quantitative polymerase chain reaction assays targeting disparate sections of EBV DNA. Fifty of the lymphomas (51%) had no amplifiable EBV DNA, and 38 lymphomas (39%) had low-level EBV infection that was deemed incidental based on EBV-encoded RNA (EBER) in situ hybridization results. The remaining 10 lymphomas (10%) had high EBV loads and EBER localization to malignant cells by EBER in situ hybridization. All 10 represented lymphoma subtypes were previously associated with EBV (Burkitt, diffuse large B-cell, or T-cell type), whereas no remnants of EBV were detected in other lymphoma subtypes (follicular, small lymphocytic, mantle cell, or marginal zone type). Interestingly, 4 of the 10 infected lymphomas had evidence of atypical viral genomes, including 3 of 4 infected T-cell lymphomas with aberrant loss of LMP2 amplicons, and a single diffuse large B-cell lymphoma lacking the central part of the viral genome spanning BamH1W, BZLF1, and EBNA1 gene segments. A reasonable screening strategy for infected malignancy involves applying EBER1 and LMP1 quantitative polymerase chain reaction assays and confirming that values exceeding 2000 copies of EBV per 100,000 cells have EBER localization to malignant cells.

  5. Analysis of API2-MALT1 fusion, trisomies, and immunoglobulin VH genes in pulmonary mucosa-associated lymphoid tissue lymphoma.

    PubMed

    Xia, Hongjing; Nakayama, Takahisa; Sakuma, Hidenori; Yamada, Seiji; Sato, Fumihiko; Takino, Hisashi; Okabe, Mitsukuni; Fujiyoshi, Yukio; Hattori, Hideo; Inagaki, Hiroshi

    2011-09-01

    Pulmonary mucosa-associated lymphoid tissue lymphoma is unique in that chronic inflammation is rare and that API2-MALT1 fusion, resulting from t(11;18)(q21;q21), occurs frequently. In this study, we examined 20 cases for API2-MALT1 fusion using the multiplex reverse-transcription polymerase chain reaction and looked for trisomy 3, trisomy 18, and abnormalities of MALT1 and IGH genes using fluorescence in situ hybridization. In addition, we analyzed VH genes by subcloning of the monoclonal polymerase chain reaction products. Of 20 cases studied, we detected gene abnormalities in 16: API2-MALT1 fusion in 9, trisomy 3 in 5, trisomy 18 in 4, MALT1 abnormality in 13, and IGH abnormality in 1. MALT1 gene abnormalities were concordant with API2-MALT1 fusion or trisomy 18. One case showed API2-MALT1 fusion and trisomy 3. On detection of API2-MALT1 fusion and trisomies, we were able to divide our cases into 3 groups, API2-MALT1 positive, trisomy positive, and no detectable gene abnormality, suggesting that tumor development had processed along different genetic pathways. All 20 cases were analyzed for VH genes. Most of the VH genes selected by the lymphomas belonged to the VH3 family, but there was no restriction to any particular VH fragment. Of interest, VH genes were unmutated in 7 cases, suggesting that T-cell-independent extrafollicular B-cell maturation may be important in the development of this lymphoma. In addition, both mutated and unmutated tumor cases were found to carry the API2-MALT1 fusion and trisomy 3. This observation suggests that these gene abnormalities may occur in microenvironments found before or outside of follicular germinal centers.

  6. [Shengqifuzheng Injection promotes the recovery of B cells in gut-associated lymphoid tissues of mice treated with cyclophosphamide].

    PubMed

    Deng, Xiangliang; Huang, Rongrong; Wen, Ruyan; Luo, Xia; Zhou, Lian

    2016-08-01

    Objective To investigate the effect of Shengqifuzheng Injection (SQFZ) on the number recovery of B cells in gut-associated lymphoid tissues (GALTs) of mice receiving cyclophosphamide-based chemotherapy. Methods BALB/c mice were randomly divided into control group, cyclophosphamide (Cy) group and SQFZ group. Mice in Cy group and SQFZ group were injected intraperitoneally with Cy (100 mg/kg), while the control mice were injected with an equal volume of normal saline. Twenty-four hours later, mice in SQFZ group were administrated intragastricly with 1 mL SQFZ once daily for 10 consecutive days, and mice in the other groups were given the same volume of normal saline. Body mass of all the mice was measured every day. Mice were killed on day 10, and the indexes of spleen and thymus were measured. Cell cycles of bone marrow cells and the percentage of B cells in lymphocytes in mesenteric lymph node (MLN) and Peyer's patch (PP) were detected by flow cytometry. In vitro, after being treated with SQFZ, activity of lymphocytes was evaluzed by MTT assay; expression of CD86 on B cell surface was analyzed by flow cytometry; and B cell proliferation was tested by carboxyfluorescein succinimidyl ester (CFSE)-based lymphocyte proliferation assay. Results SQFZ alleviated the loss of body mass caused by Cy and promoted the recovery of thymus indexes, spleen indexes and B cell number in MLN and PP. But it did not alleviate the bone marrow suppression of mice in this condition. In vitro, SQFZ enhanced lymphocyte activity, and improved the activation and proliferation of B cells. Conclusion SQFZ could accelerate the recovery of B cells in GALTs of mice receiving chemotherapy and it might act by promoting B cell proliferation.

  7. Pulmonary response to ozone: Reaction of bronchus-associated lymphoid tissue and lymph node lymphocytes in the rat

    SciTech Connect

    Dziedzic, D.; Wright, E.S.; Sargent, N.E. )

    1990-04-01

    The purpose of this work is to assess the effect of ozone, a reactive product of environmental photochemical oxidation, on lymphocytes of the lung. We exposed male Fischer rats to ozone at a concentration of 0.5 ppm for 20 hr/day for 1-14 days. Animals were treated with radioactive thymidine and were sacrificed at Day 1, 2, 3, 7, or 14 of exposure. Lungs and mediastinal lymph nodes were removed and prepared for histologic examination, evaluation of labeling indexes, and morphometric measurement. We examined two components of the lymphocyte response of the lung: the airway-related response, represented by the reaction of the bronchus-associated lymphoid tissue (BALT), and the deep lung-related response, represented by reaction of the mediastinal lymph node. Lymphocytes of both the BALT and the mediastinal lymph node showed elevated radioactive thymidine uptake; however, no evidence of cell death was observed at either site. The cells of the specialized epithelium covering the BALT (lymphoepithelium) showed increased vacuolization, indicating altered cellular function. The average size of BALTs was unchanged by ozone exposure. Under experimental conditions ozone can affect a variety of cells in the lung including bronchial epithelial cells, macrophages, and Type 1 cells. We have shown for the first time that in addition to these cells, the rat BALT also proliferates in response to ozone. In addition we confirm previous work in the mouse which shows that the mediastinal lymph node reacts as well. The airways can be affected by inflammation, can be targets of infection, and can respond to chemical irritants with bronchoconstrictive responses. They are an important target organ for hypersensitivity responses and are a primary site for pulmonary cancer formation. A role for lymphocytes has been implicated in each of these processes.

  8. Management of Suspicious Mucosa-Associated Lymphoid Tissue Lymphoma in Gastric Biopsy Specimens Obtained during Screening Endoscopy

    PubMed Central

    2016-01-01

    It is often difficult to differentiate gastric mucosa-associated lymphoid tissue (MALT) lymphoma from Helicobacter pylori-associated follicular gastritis, and thus, it becomes unclear how to manage these diseases. This study aimed to explore the management strategy for and the long-term outcomes of suspicious gastric MALT lymphoma detected by forceps biopsy during screening upper endoscopy. Between October 2003 and May 2013, consecutive subjects who were diagnosed with suspicious gastric MALT lymphomas by screening endoscopy in a health checkup program in Korea were retrospectively enrolled. Suspicious MALT lymphoma was defined as a Wotherspoon score of 3 or 4 upon pathological evaluation of the biopsy specimen. Of 105,164 subjects who underwent screening endoscopies, 49 patients with suspicious MALT lymphomas who underwent subsequent endoscopy were enrolled. Eight patients received a subsequent endoscopy without H. pylori eradication (subsequent endoscopy only group), and 41 patients received H. pylori eradication first followed by endoscopy (eradication first group). MALT lymphoma development was significantly lower in the eradication first group (2/41, 4.9%) than in the subsequent endoscopy only group (3/8, 37.5%, P = 0.026). Notably, among 35 patients with successful H. pylori eradication, there was only one MALT lymphoma patient (2.9%) in whom complete remission was achieved, and there was no recurrence during a median 45 months of endoscopic follow-up. H. pylori eradication with subsequent endoscopy would be a practical management option for suspicious MALT lymphoma detected in a forceps biopsy specimen obtained during screening upper endoscopy. PMID:27366005

  9. Association of Ig/BCL6 translocations with germinal center B lymphocytes in human lymphoid tissues: implications for malignant transformation

    PubMed Central

    Yang, Xuwei; Lee, Koutetsu; Said, Jonathan; Gong, Xun; Zhang, Ke

    2006-01-01

    Chromosomal translocations (CTs) between immunoglobulin (Ig) genes and the BCL6 proto-oncogene are frequently associated with diffuse large B-cell lymphomas (DLBCLs) and follicular lymphomas (FLs) and are implicated in the development of these lymphomas. However, whether Ig/BCL6 translocation per se is sufficient to drive malignant transformation is not clear. To understand the biology of Ig/BCL6-translocated cells prior to their malignant transformation, we developed a system capable of detecting 1 to 3 Igμ/BCL6 CT cells in 1 million mixed cells through the detection of chimeric Iμ-BCL6E2 and BCL6E1-Cμ1 transcripts that reflect reciprocal Igμ/BCL6 translocations. The chimeric transcripts that existed in the vast majority of normal lymphoid tissues are due to Igμ/BCL6 CT and were not generated from trans-splicing. Both Iμ-BCL6E2 and BCL6E1-Cμ1 transcripts were coexpressed in the same cell populations. The Ig/BCL6 recombination junctions themselves were isolated from B-cell subpopulations expressing the Iμ-BCL6 transcripts. The appearance of Igμ/BCL6 CT was associated with cells expressing germinal center but not naive B-cell markers. This study shows that Ig/BCL6 translocations occur in germinal center–stage B cells in healthy humans, and that Ig/BCL6 CTs per se are not likely sufficient to cause the malignant transformation in the context of human B cells. PMID:16728698

  10. Liposomal α-galactosylceramide is taken up by gut-associated lymphoid tissue and stimulates local and systemic immune responses.

    PubMed

    Kaneko, Kan; McDowell, Arlene; Ishii, Yasuyuki; Hook, Sarah

    2017-09-05

    α-Galactosylceramide (α-GalCer), a synthetic glycosphingolipid that exhibits potent immunostimulatory effects through activation of natural killer T (NKT) cells, can be used to treat conditions such as atopy, cancer, infection and autoimmunity. Administration of therapeutics through the oral route has advantages such as patient convenience, safety and reduced cost; however, there has been little research to investigate whether oral delivery of α-GalCer is possible. The aim of this study was therefore to determine whether α-GalCer formulated in either DMSO/Tween 80 or in liposomes, could access lymphoid tissue and stimulate immune activation following oral administration. Fluorescently labelled cationic liposomes incorporating α-GalCer were prepared, characterized and administered by oral gavage to fasted mice. Liposomes were detected inside the Peyer's patches (PPs), in the subepithelial dome just under the follicle-associated epithelium. CD11b(+) cells and CD11c(+) were shown to have taken up the formulation in a higher proportion compared to the total cell proportion in the PPs, suggesting that cells with these markers may be the prominent antigen-presenting cells involved in selective uptake. Finally, the liposomal formulation demonstrated a higher degree of immune stimulation compared to the DMSO/Tween 80 solubilized α-GalCer in the PPs, mesenteric lymph nodes and spleen as shown by the increased expression of IL-4 mRNA expression and increased proportion of NKT cells at 6 h and 3 days after administration. These results show that oral delivery of a liposomal α-GalCer can stimulate local and systemic immune responses to a different degree compared to the non-liposomal form. © 2017 Royal Pharmaceutical Society.

  11. Hypertrophy, hyperplasia, and infectious virus in gut-associated lymphoid tissue of mice after oral inoculation with simian-human or bovine-human reassortant rotaviruses.

    PubMed

    Moser, C A; Dolfi, D V; Di Vietro, M L; Heaton, P A; Offit, P A; Clark, H F

    2001-04-01

    Oral inoculation of infants with a vaccine that contains simian-human reassortant rotaviruses has been found to be a rare cause of intussusception. Because intussusception can be associated with enlargement of gut-associated lymphoid tissue, we studied the capacity of simian-human and bovine-human reassortant rotaviruses to cause lymphoid hypertrophy and hyperplasia of Peyer's patches (PP) of adult BALB/c mice. Neither hypertrophy nor hyperplasia was detected in PP after oral inoculation with simian-human or bovine-human reassortant rotaviruses. However, infectious virus was detected in PP and mesenteric lymph nodes after oral inoculation with simian, but not bovine, reassortant rotaviruses. Implications of these findings on the pathogenesis of intussusception are discussed.

  12. EBV-positive extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue in the posttransplant setting: a distinct type of posttransplant lymphoproliferative disorder?

    PubMed

    Gibson, Sarah E; Swerdlow, Steven H; Craig, Fiona E; Surti, Urvashi; Cook, James R; Nalesnik, Michael A; Lowe, Chris; Wood, Katrina M; Bacon, Chris M

    2011-06-01

    The 2008 World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues defines monomorphic posttransplant lymphoproliferative disorders (M-PTLDs) as lymphoid or plasmacytic proliferations that fulfill the criteria for one of the B-cell or T/NK-cell neoplasms recognized in immunocompetent patients. However, indolent B-cell lymphomas, such as extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma), are specifically excluded from this category. In this study, we describe the clinicopathologic features of 4 posttransplant lymphoma-like proliferations that were Epstein-Barr virus (EBV) positive, but were otherwise completely typical for a MALT lymphoma. The 4 patients (age, 12 to 71 y) had received solid organ transplants (2 hearts, 1 kidney, 1 kidney/pancreas) at a median of 116 months before presentation, and had been maintained on varying immunosuppressive regimens that included cyclosporine, azathioprine, tacrolimus, and sirolimus. Three of the 4 patients presented with solitary subcutaneous masses, whereas the fourth patient presented with a solitary orbital soft tissue mass. All the 4 cases were morphologically typical for MALT lymphoma, demonstrated plasmacytic differentiation with IgA heavy chain restriction (3 cases κ positive, 1 case λ positive), and were diffusely EBV-encoded small RNA positive. Patients were followed for a median of 44.9 months, and all achieved a complete response following various regimens that included reduced immunosuppression with or without antiviral therapy, local surgical excision, rituximab, or local radiation therapy. The uniform EBV positivity and response to immune reconstitution in some cases suggest that EBV-positive MALT lymphomas arising in the posttransplant setting should be included among PTLDs. Whether their distinctive subcutaneous/soft tissue localization and IgA positivity are uniform features will require identification of additional cases.

  13. Primary Mucosa-Associated Lymphoid Tissue Lymphoma of the Salivary Glands: A Multicenter Rare Cancer Network Study

    SciTech Connect

    Anacak, Yavuz; Miller, Robert C.; Constantinou, Nikos; Mamusa, Angela M.; Epelbaum, Ron; Li Yexiong; Calduch, Anna Lucas; Kowalczyk, Anna; Weber, Damien C.; Kadish, Sidney P.; Poortmans, Philip; Kamer, Serra; Ozsahin, Mahmut

    2012-01-01

    Purpose: Involvement of salivary glands with mucosa-associated lymphoid tissue (MALT) lymphoma is rare. This retrospective study was performed to assess the clinical profile, treatment outcome, and prognostic factors of MALT lymphoma of the salivary glands. Methods and Materials: Thirteen member centers of the Rare Cancer Network from 10 countries participated, providing data on 63 patients. The median age was 58 years; 47 patients were female and 16 were male. The parotid glands were involved in 49 cases, submandibular in 15, and minor glands in 3. Multiple glands were involved in 9 patients. Staging was as follows: IE in 34, IIE in 12, IIIE in 2, and IV in 15 patients. Results: Surgery (S) alone was performed in 9, radiotherapy (RT) alone in 8, and chemotherapy (CT) alone in 4 patients. Forty-one patients received combined modality treatment (S + RT in 23, S + CT in 8, RT + CT in 4, and all three modalities in 6 patients). No active treatment was given in one case. After initial treatment there was no tumor in 57 patients and residual tumor in 5. Tumor progression was observed in 23 (36.5%) (local in 1, other salivary glands in 10, lymph nodes in 11, and elsewhere in 6). Five patients died of disease progression and the other 5 of other causes. The 5-year disease-free survival, disease-specific survival, and overall survival were 54.4%, 93.2%, and 81.7%, respectively. Factors influencing disease-free survival were use of RT, stage, and residual tumor (p < 0.01). Factors influencing disease-specific survival were stage, recurrence, and residual tumor (p < 0.01). Conclusions: To our knowledge, this report represents the largest series of MALT lymphomas of the salivary glands published to date. This disease may involve all salivary glands either initially or subsequently in 30% of patients. Recurrences may occur in up to 35% of patients at 5 years; however, survival is not affected. Radiotherapy is the only treatment modality that improves disease-free survival.

  14. Modeling [(18)F]-FDG lymphoid tissue kinetics to characterize nonhuman primate immune response to Middle East respiratory syndrome-coronavirus aerosol challenge.

    PubMed

    Chefer, Svetlana; Thomasson, David; Seidel, Jurgen; Reba, Richard C; Bohannon, J Kyle; Lackemeyer, Mathew G; Bartos, Chris; Sayre, Philip J; Bollinger, Laura; Hensley, Lisa E; Jahrling, Peter B; Johnson, Reed F

    2015-12-01

    The pathogenesis and immune response to Middle East respiratory syndrome (MERS) caused by a recently discovered coronavirus, MERS-CoV, have not been fully characterized because a suitable animal model is currently not available. (18)F-Fluorodeoxyglucose ([(18)F]-FDG)-positron emission tomography/computed tomography (PET/CT) as a longitudinal noninvasive approach can be beneficial in providing biomarkers for host immune response. [(18)F]-FDG uptake is increased in activated immune cells in response to virus entry and can be localized by PET imaging. We used [(18)F]-FDG-PET/CT to investigate the host response developing in nonhuman primates after MERS-CoV exposure and applied kinetic modeling to monitor the influx rate constant (K i ) in responsive lymphoid tissue. Multiple [(18)F]-FDG-PET and CT images were acquired on a PET/CT clinical scanner modified to operate in a biosafety level 4 environment prior to and up to 29 days after MERS-CoV aerosol exposure. Time activity curves of various lymphoid tissues were reconstructed to follow the [(18)F]-FDG uptake for approximately 60 min (3,600 s). Image-derived input function was used to calculate K i for lymphoid tissues by Patlak plot. Two-way repeated measures analysis of variance revealed alterations in K i that was associated with the time point (p < 0.001) after virus exposure and the location of lymphoid tissue (p = 0.0004). As revealed by a statistically significant interaction (p < 0.0001) between these two factors, the pattern of K i changes over time differed between three locations but not between subjects. A distinguished pattern of statistically significant elevation in K i was observed in mediastinal lymph nodes (LNs) that correlated to K i changes in axillary LNs. Changes in LNs K i were concurrent with elevations of monocytes in peripheral blood. [(18)F]-FDG-PET is able to detect subtle changes in host immune response to contain a subclinical virus infection. Full quantitative analysis is

  15. Pulmonary Mucosa-associated Lymphoid Tissue Lymphoma with Spontaneous Regression after Computed Tomography-guided Needle Biopsy: A Case Report and Summary of 8 Reported Cases.

    PubMed

    Fukushima, Kazuaki; Hirosako, Susumu; Tenjin, Yuki; Mukasa, Yosuke; Kojima, Keisuke; Saeki, Sho; Okamoto, Shinichiro; Ichiyasu, Hidenori; Fujii, Kazuhiko; Kikukawa, Yoshitaka; Kawanaka, Koichi; Kohrogi, Hirotsugu

    A 72-year-old woman was admitted to our hospital with a solitary right lung nodule. She had no symptoms and no abnormal physical findings except for bladder cancer. Tumor markers were mildly elevated but no other abnormal laboratory data were found. The nodule was diagnosed to be pulmonary mucosa-associated lymphoid tissue lymphoma on computed tomography-guided needle biopsy. Thereafter, she first underwent surgery for bladder cancer. The lung nodule was found to have slightly increased at three months and then disappeared at 15 months after the biopsy. The notable clinical course of this rare disease suggests the effectiveness of a non-interventional treatment strategy.

  16. Pulmonary Mucosa-associated Lymphoid Tissue Lymphoma with Spontaneous Regression after Computed Tomography-guided Needle Biopsy: A Case Report and Summary of 8 Reported Cases

    PubMed Central

    Fukushima, Kazuaki; Hirosako, Susumu; Tenjin, Yuki; Mukasa, Yosuke; Kojima, Keisuke; Saeki, Sho; Okamoto, Shinichiro; Ichiyasu, Hidenori; Fujii, Kazuhiko; Kikukawa, Yoshitaka; Kawanaka, Koichi; Kohrogi, Hirotsugu

    2016-01-01

    A 72-year-old woman was admitted to our hospital with a solitary right lung nodule. She had no symptoms and no abnormal physical findings except for bladder cancer. Tumor markers were mildly elevated but no other abnormal laboratory data were found. The nodule was diagnosed to be pulmonary mucosa-associated lymphoid tissue lymphoma on computed tomography-guided needle biopsy. Thereafter, she first underwent surgery for bladder cancer. The lung nodule was found to have slightly increased at three months and then disappeared at 15 months after the biopsy. The notable clinical course of this rare disease suggests the effectiveness of a non-interventional treatment strategy. PMID:27980268

  17. Influence of age, sex and rearing systems on Toll-like receptor 7 (TLR7) expression pattern in gut, lung and lymphoid tissues of indigenous ducks.

    PubMed

    Kolluri, Gautham; Ramamurthy, N; Churchil, R R; Dhinakar Raj, G; Kannaki, T R

    2014-02-01

    Abstract 1. The objective of the experiment was to determine the influence of age, sex and rearing system on Toll-like receptor 7 (TLR7) gene expression in gut, lung and lymphoid tissues and physiological responses to stress in male and female indigenous ducks of Tamil Nadu, India. 2. A total of 36 ducks (12 males and 24 females) were obtained from local farmers and tissue samples of gut tissues (duodenum, jejunum, ileum and caecum), lymphoid organs (spleen and bursa) and lungs were collected in RNAlater solution followed by RNA extraction. 3. After normalisation to β-actin (endogenous control) qPCR analysis identified a significant effect of age, sex and rearing system on TLR7 expression in the ducks. 4. A significant up-regulation of TLR7 expression was observed in lungs, duodenum, jejunum, ileum and caecum of sexually mature (45 wk) compared with that of immature ducks (16 wk). Among sexes, male ducks had significantly higher TLR7 expression than female ducks. 5. Age and sex interactions were significant in lungs, duodenum, jejunum and caecum. Ducks reared in an extensive housing system showed significantly higher TLR7 expression in bursa, lungs, duodenum, ileum and caecum compared to intensively reared ducks. There were no effects of age, sex and rearing systems on TLR7 expression in the spleen. 6. The heterophil-to-lymphocyte ratio and serum corticosterone were higher in ducks reared on an intensive system compared with ducks from an extensive rearing system.

  18. Bioengineering of Artificial Lymphoid Organs

    PubMed Central

    Nosenko, M. A.; Drutskaya, M. S.; Moisenovich, M. M.; Nedospasov, S. A.

    2016-01-01

    This review addresses the issue of bioengineering of artificial lymphoid organs.Progress in this field may help to better understand the nature of the structure-function relations that exist in immune organs. Artifical lymphoid organs may also be advantageous in the therapy or correction of immunodefficiencies, autoimmune diseases, and cancer. The structural organization, development, and function of lymphoid tissue are analyzed with a focus on the role of intercellular contacts and on the cytokine signaling pathways regulating these processes. We describe various polymeric materials, as scaffolds, for artificial tissue engineering. Finally, published studies in which artificial lymphoid organs were generated are reviewed and possible future directions in the field are discussed. PMID:27437136

  19. Human innate lymphoid cells.

    PubMed

    Mjösberg, Jenny; Spits, Hergen

    2016-11-01

    Innate lymphoid cells (ILCs) are increasingly acknowledged as important mediators of immune homeostasis and pathology. ILCs act as early orchestrators of immunity, responding to epithelium-derived signals by expressing an array of cytokines and cell-surface receptors, which shape subsequent immune responses. As such, ILCs make up interesting therapeutic targets for several diseases. In patients with allergy and asthma, group 2 innate lymphoid cells produce high amounts of IL-5 and IL-13, thereby contributing to type 2-mediated inflammation. Group 3 innate lymphoid cells are implicated in intestinal homeostasis and psoriasis pathology through abundant IL-22 production, whereas group 1 innate lymphoid cells are accumulated in chronic inflammation of the gut (inflammatory bowel disease) and lung (chronic obstructive pulmonary disease), where they contribute to IFN-γ-mediated inflammation. Although the ontogeny of mouse ILCs is slowly unraveling, the development of human ILCs is far from understood. In addition, the growing complexity of the human ILC family in terms of previously unrecognized functional heterogeneity and plasticity has generated confusion within the field. Here we provide an updated view on the function and plasticity of human ILCs in tissue homeostasis and disease. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  20. Activation of NF-kappaB and inhibition of p53-mediated apoptosis by API2/mucosa-associated lymphoid tissue 1 fusions promote oncogenesis.

    PubMed

    Stoffel, Archontoula; Chaurushiya, Mira; Singh, Bhuvanesh; Levine, Arnold J

    2004-06-15

    Mucosa-associated lymphoid tissue (MALT) lymphoma is the most common extranodal lymphoid cell neoplasia; it frequently follows chronic bacteria-induced inflammation in various tissues. MALT lymphomas are characterized genetically by the t(11;18)(q21;q21) translocation, which yields chimeric transcripts encoding structurally distinct API2/MALT1 fusion proteins. In this study, we provide functional evidence for the contribution of API2/MALT1 fusion proteins to transformation of cells in culture by activating the NF-kappaB pathway through a RelB/p50 dimer. Using microchip gene expression analysis, we demonstrate that different forms of the API2/MALT1 proteins activate both unique and overlapping gene programs in cells. In addition to this genome reprogramming, expression of distinct API2/MALT1 fusion products inhibits DNA damage-induced, p53-mediated apoptosis in an NF-kappaB-dependent manner. Collectively, these data reveal previously unknown functional diversity among API2/MALT1 fusion products and their function in NF-kappaB signaling as it connects to the apoptotic program, a pathway with strong relevance to cancer. Furthermore, they provide evidence underlying the emerging role of the NF-kappaB signaling pathway in the inhibition of apoptosis.

  1. Selective chemotaxis of subsets of B lymphocytes from gut-associated lymphoid tissue and its implications for the recruitment of mucosal plasma cells.

    PubMed

    Czinn, S J; Lamm, M E

    1986-05-15

    As they differentiate, precursor cells from the gut-associated lymphoid tissue are known to travel via the lymphatic system to the blood and then preferentially to home to various mucosal and exocrine sites such as the lamina propria of the gut and the lactating mammary gland, where they give rise to IgA-secreting plasma cells. The present study, directed at the mechanism by which the circulating precursors of mucosal IgA plasma cells selectively lodge in characteristic locations, explored the hypothesis that such homing is due to a locally produced chemotactic factor and that milk might be a source of such a factor. Subsets of lymphocytes bearing particular surface markers and purified by panning from lymph nodes of mice were examined in a micropore chemotaxis assay to search for the presence of chemotactic activity in mouse milk. The globulin fraction of whey was shown to contain a nondialyzable factor that is chemotactic for IgA (and also IgG)-positive lymphocytes when these are obtained from mesenteric lymph nodes as a source of mucosal-associated lymphoid tissue. Lymphocytes from peripheral lymph nodes, nonmucosal associated, were unaffected as were surface IgM-positive lymphocytes and T lymphocytes obtained from mesenteric nodes. Chemotactic activity for IgA lymphocytes was undetectable in mouse serum. The data are consistent with the idea that precursors of mucosal IgA plasma cells home to mucosal and exocrine sites in response to a specific chemotactic factor elaborated by local differentiated epithelial cells.

  2. Gut-Associated Lymphoid Tissue: A Key Tissue Inside the Mucosal Immune System of Hens Immunized with Escherichia coli F4.

    PubMed

    Peralta, Maria F; Magnoli, Alejandra; Alustiza, Fabrisio; Nilson, Armando; Miazzo, Raúl; Vivas, Adriana

    2017-01-01

    Immunoglobulin Y (IgY) is the predominant antibody found in hen's (Gallus domesticus) egg yolk. This antibody, developed against several microorganisms in hen egg yolk, has been successfully used as an alternative to immunoglobulins from mammals for use in immunodiagnostics and immunotherapy. Enteropathogenic Escherichia coli (E.coli) F4 is the main etiological agent associated with swine neonatal diarrhea, and it causes notable economic losses in swine production. The aim of the present study was to evaluate the relationship between humoral immune response and the activation of gut-associated lymphoid tissue (GALT) in laying hens intramuscularly immunized with E. coli F4. Adult laying Shaver hens were immunized with a bacterin based on an inactivated lysate E. coli F4 strain that was originally isolated from neonatal piglet diarrhea, following a recommended schedule. The percentage of B lymphocytes in blood and spleen homogenates was determined by flow cytometry. Villi histomorphometry and the size of germinal centers (GC) activated in GALT and the spleen were measured in histological samples either stained with hematoxylin/eosin or through immunofluorescence. Antibody and isotype-specific antibodies in serum and egg yolk were measured using indirect enzyme-linked immunosorbent assay (ELISA). Secretory and serum immunoglobulin A (IgA) were measured by ELISA tests. Laying hen with intramuscular immunization with E. coli F4 lysate, activated both mucosal and systemic protection. Mucosal protection was provided through B lymphocytes, and most of them were activated on Peyer's patches and esophageal tonsils, in GALT. Furthermore, increased B lymphocyte number in the lamina propria of the gut, and increased intraepithelial plasmatic cell number, produced high levels of mucosal IgA. Activated B lymphocytes interacted with absorptive cells, immune cells, and microbiota in the gut, producing signals that were translated into a powerful physical defense by producing a

  3. Gut-Associated Lymphoid Tissue: A Key Tissue Inside the Mucosal Immune System of Hens Immunized with Escherichia coli F4

    PubMed Central

    Peralta, Maria F.; Magnoli, Alejandra; Alustiza, Fabrisio; Nilson, Armando; Miazzo, Raúl; Vivas, Adriana

    2017-01-01

    Immunoglobulin Y (IgY) is the predominant antibody found in hen’s (Gallus domesticus) egg yolk. This antibody, developed against several microorganisms in hen egg yolk, has been successfully used as an alternative to immunoglobulins from mammals for use in immunodiagnostics and immunotherapy. Enteropathogenic Escherichia coli (E.coli) F4 is the main etiological agent associated with swine neonatal diarrhea, and it causes notable economic losses in swine production. The aim of the present study was to evaluate the relationship between humoral immune response and the activation of gut-associated lymphoid tissue (GALT) in laying hens intramuscularly immunized with E. coli F4. Adult laying Shaver hens were immunized with a bacterin based on an inactivated lysate E. coli F4 strain that was originally isolated from neonatal piglet diarrhea, following a recommended schedule. The percentage of B lymphocytes in blood and spleen homogenates was determined by flow cytometry. Villi histomorphometry and the size of germinal centers (GC) activated in GALT and the spleen were measured in histological samples either stained with hematoxylin/eosin or through immunofluorescence. Antibody and isotype-specific antibodies in serum and egg yolk were measured using indirect enzyme-linked immunosorbent assay (ELISA). Secretory and serum immunoglobulin A (IgA) were measured by ELISA tests. Laying hen with intramuscular immunization with E. coli F4 lysate, activated both mucosal and systemic protection. Mucosal protection was provided through B lymphocytes, and most of them were activated on Peyer’s patches and esophageal tonsils, in GALT. Furthermore, increased B lymphocyte number in the lamina propria of the gut, and increased intraepithelial plasmatic cell number, produced high levels of mucosal IgA. Activated B lymphocytes interacted with absorptive cells, immune cells, and microbiota in the gut, producing signals that were translated into a powerful physical defense by producing a

  4. CD56(bright)perforin(low) noncytotoxic human NK cells are abundant in both healthy and neoplastic solid tissues and recirculate to secondary lymphoid organs via afferent lymph.

    PubMed

    Carrega, Paolo; Bonaccorsi, Irene; Di Carlo, Emma; Morandi, Barbara; Paul, Petra; Rizzello, Valeria; Cipollone, Giuseppe; Navarra, Giuseppe; Mingari, Maria Cristina; Moretta, Lorenzo; Ferlazzo, Guido

    2014-04-15

    As limited information is available regarding the distribution and trafficking of NK cells among solid organs, we have analyzed a wide array of tissues derived from different human compartments. NK cells were widely distributed in most solid tissues, although their amount varied significantly depending on the tissue/organ analyzed. Interestingly, the distribution appeared to be subset specific, as some tissues were preferentially populated by CD56(bright)perforin(low) NK cells, with others by the CD56(dim)perforin(high) cytotoxic counterpart. Nevertheless, most tissues were highly enriched in CD56(bright)perforin(low) cells, and the distribution of NK subsets appeared in accordance with tissue gene expression of chemotactic factors, for which receptors are differently represented in the two subsets. Remarkably, chemokine expression pattern of tissues was modified after neoplastic transformation. As a result, although the total amount of NK cells infiltrating the tissues did not significantly change upon malignant transformation, the relative proportion of NK subsets infiltrating the tissues was different, with a trend toward a tumor-infiltrating NK population enriched in noncytotoxic cells. Besides solid tissues, CD56(bright)perforin(low) NK cells were also detected in seroma fluids, which represents an accrual of human afferent lymph, indicating that they may leave peripheral solid tissues and recirculate to secondary lymphoid organs via lymphatic vessels. Our results provide a comprehensive mapping of NK cells in human tissues, demonstrating that discrete NK subsets populate and recirculate through most human tissues and that organ-specific chemokine expression patterns might affect their distribution. In this context, chemokine switch upon neoplastic transformation might represent a novel mechanism of tumor immune escape.

  5. Flagellin modulates functions of the follicle-associated epithelium to facilitate uptake of particles into organized mucosal lymphoid tissues

    PubMed Central

    Chabot, Sophie M.; Shawi, May; Eaves-Pyles, Tonyia; Neutra, Marian R.

    2016-01-01

    Bacterial flagellin activates innate immune responses by signaling through TLR5, and is a potential vaccine adjuvant. Mucosal lymphoid follicles, inductive sites for adaptive mucosal immune responses, are covered by a follicle-associated epithelium (FAE) specialized for uptake of antigens. This study demonstrates that mucosal application of S.dublin flagellin enhanced transepithelial transport of microparticles by the FAE of mouse Peyer's patch in vivo. Flagellin also induced rapid, matrix metalloproteinase-dependent migration of subepithelial dendritic cells (DCs) into the FAE, better positioning DCs for antigen capture. These innate responses to flagellin enhance FAE functions and may promote adaptive immune responses in the mucosa. PMID:18721059

  6. Chemokine receptor CXCR5 supports solitary intestinal lymphoid tissue formation, B cell homing, and induction of intestinal IgA responses.

    PubMed

    Velaga, Sarvari; Herbrand, Heike; Friedrichsen, Michaela; Jiong, Tian; Dorsch, Martina; Hoffmann, Matthias W; Förster, Reinhold; Pabst, Oliver

    2009-03-01

    Solitary intestinal lymphoid tissue (SILT) comprises a spectrum of phenotypically diverse lymphoid aggregates interspersed throughout the small intestinal mucosa. Manifestations of SILT range from tiny lymphoid aggregates almost void of mature lymphocytes to large structures dominated by B cells. Large SILT phenotypically resemble a single Peyer's patch follicle, suggesting that SILT might contribute to intestinal humoral immune responses. In this study, we track the fate of individual SILT in vivo over time and analyze SILT formation and function in chemokine receptor CXCR5-deficient mice. We show that, in analogy to Peyer's patches, formation of SILT is invariantly determined during ontogeny and depends on CXCR5. Young CXCR5-deficient mice completely lack SILT, suggesting that CXCR5 is essential for SILT formation during regular postnatal development. However, microbiota and other external stimuli can induce the formation of aberrant SILT distinguished by impaired development of B cell follicles in CXCR5-deficient mice. Small intestinal transplantation and bone marrow transplantation reveal that defect follicle formation is due to impaired B cell homing. Moreover, oral immunization with cholera toxin or infection with noninvasive Salmonella fail to induce efficient humoral immune responses in CXCR5-deficient mice. Bone marrow transplantation of CXCR5-deficient recipients with wild-type bone marrow rescued B cell follicle formation in SILT but failed to restore full humoral immune responses. These results reveal an essential role of CXCR5 in Peyer's patch and SILT development and function and indicate that SILT do not fully compensate for the lack of Peyer's patches in T cell-dependent humoral immune responses.

  7. Nanodrug formulations to enhance HIV drug exposure in lymphoid tissues and cells: clinical significance and potential impact on treatment and eradication of HIV/AIDS

    PubMed Central

    Shao, Jingwei; Kraft, John C; Li, Bowen; Yu, Jesse; Freeling, Jennifer; Koehn, Josefin; Ho, Rodney JY

    2016-01-01

    Although oral combination antiretroviral therapy effectively clears plasma HIV, patients on oral drugs exhibit much lower drug concentrations in lymph nodes than blood. This drug insufficiency is linked to residual HIV in cells of lymph nodes. While nanoformulations improve drug solubility, safety and delivery, most HIV nanoformulations are intended to extend plasma levels. A stable nanodrug combination that transports, delivers and accumulates in lymph nodes is needed to clear HIV in lymphoid tissues. This review discusses limitations of current oral combination antiretroviral therapy and advances in anti-HIV nanoformulations. A ‘systems approach’ has been proposed to overcome these limitations. This concept has been used to develop nanoformulations for overcoming drug insufficiency, extending cell and tissue exposure and clearing virus for treating HIV/AIDS. PMID:26892323

  8. Deciphering alternative splicing and nonsense-mediated decay modulate expression in primary lymphoid tissues of birds infected with avian pathogenic E. coli (APEC).

    PubMed

    Sun, Hongyan

    2017-03-07

    Avian pathogenic E. coli (APEC) can lead to a loss in millions of dollars in poultry annually because of mortality and produce contamination. Studies have verified that many immune-related genes undergo changes in alternative splicing (AS), along with nonsense mediated decay (NMD), to regulate the immune system under different conditions. Therefore, the splicing profiles of primary lymphoid tissues with systemic APEC infection need to be comprehensively examined. Gene expression in RNAseq data were obtained for three different immune tissues (bone marrow, thymus, and bursa) from three phenotype birds (non-challenged, resistant, and susceptible birds) at two time points. Alternative 5' splice sites and exon skipping/inclusion were identified as the major alternative splicing events in avian primary immune organs under systemic APEC infection. In this study, we detected hundreds of differentially-expressed-transcript-containing genes (DETs) between different phenotype birds at 5 days post-infection (dpi). DETs, PSAP and STT3A, with NMD have important functions under systemic APEC infection. DETs, CDC45, CDK1, RAG2, POLR1B, PSAP, and DNASE1L3, from the same transcription start sites (TSS) indicate that cell death, cell cycle, cellular function, and maintenance were predominant in host under systemic APEC. With the use of RNAseq technology and bioinformatics tools, this study provides a portrait of the AS event and NMD in primary lymphoid tissues, which play critical roles in host homeostasis under systemic APEC infection. According to this study, AS plays a pivotal regulatory role in the immune response in chicken under systemic APEC infection via either NMD or alternative TSSs. This study elucidates the regulatory role of AS for the immune complex under systemic APEC infection.

  9. Compartmentalization of SIV Replication Within Secondary Lymphoid Tissues of Rhesus Macaques is Linked to Disease Stage and Inversely Related to Localization of Virus-Specific CTL1 2

    PubMed Central

    Connick, Elizabeth; Folkvord, Joy M.; Lind, Katherine T.; Rakasz, Eva G.; Miles, Brodie; Wilson, Nancy A.; Santiago, Mario L.; Schmitt, Kimberly; Stephens, Edward B.; Kim, Hyeon O.; Wagstaff, Reece; Li, Shengbin; Abdelaal, Hadia M.; Kemp, Nathan; Watkins, David I.; MaWhinney, Samantha; Skinner, Pamela J.

    2014-01-01

    We previously demonstrated that HIV replication is concentrated in lymph node B cell follicles during chronic infection and that HIV-specific CTL fail to accumulate in large numbers at those sites. It is unknown whether these observations can be generalized to other secondary lymphoid tissues, or whether virus compartmentalization occurs in the absence of CTL. We evaluated these questions in SIVmac239-infected rhesus macaques by quantifying SIV RNA+ cells and SIV-specific CTL in situ in spleen, lymph nodes and intestinal tissues obtained at several stages of infection. During chronic asymptomatic infection prior to simian AIDS (SAIDS), SIV-producing cells were more concentrated in follicular compared to extrafollicular regions of secondary lymphoid tissues. At day 14 of infection, when CTL have minimal impact on virus replication, there was no compartmentalization of SIV-producing cells. Virus compartmentalization was diminished in animals with SAIDS, which often have low frequency CTL responses. SIV-specific CTL were consistently more concentrated within extrafollicular regions of lymph node and spleen in chronically infected animals regardless of epitope specificity. Frequencies of SIV-specific CTL within follicular and extrafollicular compartments predicted SIV RNA+ cells within these compartments in a mixed model. Few SIV-specific CTL expressed the follicular homing molecule CXCR5 in the absence of the extrafollicular retention molecule CCR7, possibly accounting for the paucity of follicular CTL. These findings bolster the hypothesis that B cell follicles are immune privileged sites and suggest that strategies to augment CTL in B cell follicles could lead to improved viral control and possibly a functional cure for HIV infection. PMID:25362178

  10. Epstein-barr virus-associated extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT Lymphoma) arising in the parotid gland of a child with ataxia telangiectasia.

    PubMed

    Bennett, Jennifer A; Bayerl, Michael G

    2015-03-01

    Hematologic malignancies, in particular T-cell lymphomas/leukemias, are prevalent in patients with ataxia telangiectasia (AT), with most reported cases being clinically aggressive and high grade. Epstein-Barr virus (EBV) is often associated with lymphoid proliferations/neoplasms arising in immunodeficient patients. Reports of low-grade B-cell neoplasms in the ataxia telangiectasia population are extremely rare. Here, we describe a case of EBV-associated extranodal marginal zone lymphoma (mucosa-associated lymphoid tissue lymphoma) of the parotid gland in a 16-year-old boy with AT. In addition, we review the literature of hematologic malignancies in the AT population as well as the occurrence of EBV in mucosa-associated lymphoid tissue lymphoma.

  11. Primary B-Cell Mucosa-Associated Lymphoid Tissue Lymphoma of the Hard Palate and Parotid Gland: Report of One Case and Review of the Literature.

    PubMed

    Yonal-Hindilerden, Ipek; Hindilerden, Fehmi; Arslan, Serkan; Turan-Guzel, Nalan; Dogan, Ibrahim Oner; Nalcaci, Meliha

    2016-11-01

    A 61-year-old woman was admitted to our hospital with an ulcerated palate mass and swelling of the right parotid gland. Incisional biopsy from the hard palate revealed an extranodal marginal zone B-cell lymphoma, also called mucosa-associated lymphoid tissue (MALT) lymphoma. Final diagnosis was MALT lymphoma of the parotid gland with concomitant involvement of an extremely seldom site of involvement: the hard palate. To our knowledge, this report illustrates the first case of MALT lymphoma of the hard palate and parotid gland without an underlying autoimmune disease. Rituximab-based combination regimen (R-CHOP) provided complete remission with total regression of mass lesions at the hard palate and parotid gland. At 44-month follow-up, there is no disease relapse. We adressed the manifestations and management of MALT lymphoma patients with involvement of salivary gland and oral cavity.

  12. Chronic stress induces structural alterations in splenic lymphoid tissue that are associated with changes in corticosterone levels in wistar-kyoto rats.

    PubMed

    Hernandez, María Eugenia; Martinez-Mota, Lucia; Salinas, Citlaltepetl; Marquez-Velasco, Ricardo; Hernandez-Chan, Nancy G; Morales-Montor, Jorge; Pérez-Tapia, Mayra; Streber, María L; Granados-Camacho, Ivonne; Becerril, Enrique; Javier, Baquera-Heredia; Pavón, Lenin

    2013-01-01

    Major depressive disorder patients present chronic stress and decreased immunity. The Wistar-Kyoto rat (WKY) is a strain in which the hypothalamic-pituitary-adrenal axis is overactivated. To determine whether chronic stress induces changes in corticosterone levels and splenic lymphoid tissue, 9-week-old male rats were subject to restraint stress (3 h daily), chemical stress (hydrocortisone treatment, 50 mg/Kg weight), mixed stress (restraint plus hydrocortisone), or control treatment (without stress) for 1, 4, and 7 weeks. The serum corticosterone levels by RIA and spleens morphology were analyzed. Corticosterone levels as did the structure, size of the follicles and morphology of the parenchyma (increase in red pulp) in the spleen, varied depending on time and type of stressor. These changes indicate that chronic stress alters the immune response in the spleen in WKY rats by inducing morphological changes, explaining in part the impaired immunity that develops in organisms that are exposed to chronic stress.

  13. Primary B-Cell Mucosa-Associated Lymphoid Tissue Lymphoma of the Hard Palate and Parotid Gland: Report of One Case and Review of the Literature

    PubMed Central

    Yonal-Hindilerden, Ipek; Hindilerden, Fehmi; Arslan, Serkan; Turan-Guzel, Nalan; Dogan, Ibrahim Oner; Nalcaci, Meliha

    2016-01-01

    A 61-year-old woman was admitted to our hospital with an ulcerated palate mass and swelling of the right parotid gland. Incisional biopsy from the hard palate revealed an extranodal marginal zone B-cell lymphoma, also called mucosa-associated lymphoid tissue (MALT) lymphoma. Final diagnosis was MALT lymphoma of the parotid gland with concomitant involvement of an extremely seldom site of involvement: the hard palate. To our knowledge, this report illustrates the first case of MALT lymphoma of the hard palate and parotid gland without an underlying autoimmune disease. Rituximab-based combination regimen (R-CHOP) provided complete remission with total regression of mass lesions at the hard palate and parotid gland. At 44-month follow-up, there is no disease relapse. We adressed the manifestations and management of MALT lymphoma patients with involvement of salivary gland and oral cavity. PMID:27738485

  14. Localization of collagen modifying enzymes on fibroblastic reticular cells and follicular dendritic cells in non-neoplastic and neoplastic lymphoid tissues.

    PubMed

    Ohe, Rintaro; Aung, Naing Ye; Meng, Hongxue; Kabasawa, Takanobu; Suto, Aya; Tamazawa, Nobuyuki; Yang, Suran; Kato, Tomoya; Yamakawa, Mitsunori

    2016-07-01

    The aim of this study was to evaluate the localization of collagen modifying enzymes (CMEs) on fibroblastic reticular cells (FRCs) and follicular dendritic cells (FDCs) in non-neoplastic lymphoid tissues and various malignant lymphomas. The expression of prolyl 4-hydroxylase 1 (P4H1), lysyl hydroxylase 3 (LH3), and protein disulfide isomerase (PDI) was frequently observed on FRCs and FDCs in the germinal center (GC), except for the mantle zone. The expression of CMEs was lower in most lymphomas than in their respective postulated normal counterparts. The ratio of transglutaminase II(+) FRCs/CD35(+) FDCs was also lower in follicular lymphomas (FL) than in other lymphomas. The mRNAs of some CMEs (P4H1, prolyl 4-hydroxylase 3, LH3, and heat shock protein 47) were confirmed in almost all lymphomas. These results indicate that lymphoma cell proliferation suppresses/decreases the number of CMEs expressing FRCs and FDCs in most lymphomas.

  15. Localization of collagen modifying enzymes on fibroblastic reticular cells and follicular dendritic cells in non-neoplastic and neoplastic lymphoid tissues

    PubMed Central

    Ohe, Rintaro; Aung, Naing Ye; Meng, Hongxue; Kabasawa, Takanobu; Suto, Aya; Tamazawa, Nobuyuki; Yang, Suran; Kato, Tomoya; Yamakawa, Mitsunori

    2016-01-01

    Abstract The aim of this study was to evaluate the localization of collagen modifying enzymes (CMEs) on fibroblastic reticular cells (FRCs) and follicular dendritic cells (FDCs) in non-neoplastic lymphoid tissues and various malignant lymphomas. The expression of prolyl 4-hydroxylase 1 (P4H1), lysyl hydroxylase 3 (LH3), and protein disulfide isomerase (PDI) was frequently observed on FRCs and FDCs in the germinal center (GC), except for the mantle zone. The expression of CMEs was lower in most lymphomas than in their respective postulated normal counterparts. The ratio of transglutaminase II+ FRCs/CD35+ FDCs was also lower in follicular lymphomas (FL) than in other lymphomas. The mRNAs of some CMEs (P4H1, prolyl 4-hydroxylase 3, LH3, and heat shock protein 47) were confirmed in almost all lymphomas. These results indicate that lymphoma cell proliferation suppresses/decreases the number of CMEs expressing FRCs and FDCs in most lymphomas. PMID:26700650

  16. Complex expression patterns of lymphocyte-specific genes during the development of cartilaginous fish implicate unique lymphoid tissues in generating an immune repertoire

    NASA Technical Reports Server (NTRS)

    Miracle, A. L.; Anderson, M. K.; Litman, R. T.; Walsh, C. J.; Luer, C. A.; Rothenberg, E. V.; Litman, G. W.

    2001-01-01

    Cartilaginous fish express canonical B and T cell recognition genes, but their lymphoid organs and lymphocyte development have been poorly defined. Here, the expression of Ig, TCR, recombination-activating gene (Rag)-1 and terminal deoxynucleosidase (TdT) genes has been used to identify roles of various lymphoid tissues throughout development in the cartilaginous fish, Raja eglanteria (clearnose skate). In embryogenesis, Ig and TCR genes are sharply up-regulated at 8 weeks of development. At this stage TCR and TdT expression is limited to the thymus; later, TCR gene expression appears in peripheral sites in hatchlings and adults, suggesting that the thymus is a source of T cells as in mammals. B cell gene expression indicates more complex roles for the spleen and two special organs of cartilaginous fish-the Leydig and epigonal (gonad-associated) organs. In the adult, the Leydig organ is the site of the highest IgM and IgX expression. However, the spleen is the first site of IgM expression, while IgX is expressed first in gonad, liver, Leydig and even thymus. Distinctive spatiotemporal patterns of Ig light chain gene expression also are seen. A subset of Ig genes is pre-rearranged in the germline of the cartilaginous fish, making expression possible without rearrangement. To assess whether this allows differential developmental regulation, IgM and IgX heavy chain cDNA sequences from specific tissues and developmental stages have been compared with known germline-joined genomic sequences. Both non-productively rearranged genes and germline-joined genes are transcribed in the embryo and hatchling, but not in the adult.

  17. Complex expression patterns of lymphocyte-specific genes during the development of cartilaginous fish implicate unique lymphoid tissues in generating an immune repertoire

    NASA Technical Reports Server (NTRS)

    Miracle, A. L.; Anderson, M. K.; Litman, R. T.; Walsh, C. J.; Luer, C. A.; Rothenberg, E. V.; Litman, G. W.

    2001-01-01

    Cartilaginous fish express canonical B and T cell recognition genes, but their lymphoid organs and lymphocyte development have been poorly defined. Here, the expression of Ig, TCR, recombination-activating gene (Rag)-1 and terminal deoxynucleosidase (TdT) genes has been used to identify roles of various lymphoid tissues throughout development in the cartilaginous fish, Raja eglanteria (clearnose skate). In embryogenesis, Ig and TCR genes are sharply up-regulated at 8 weeks of development. At this stage TCR and TdT expression is limited to the thymus; later, TCR gene expression appears in peripheral sites in hatchlings and adults, suggesting that the thymus is a source of T cells as in mammals. B cell gene expression indicates more complex roles for the spleen and two special organs of cartilaginous fish-the Leydig and epigonal (gonad-associated) organs. In the adult, the Leydig organ is the site of the highest IgM and IgX expression. However, the spleen is the first site of IgM expression, while IgX is expressed first in gonad, liver, Leydig and even thymus. Distinctive spatiotemporal patterns of Ig light chain gene expression also are seen. A subset of Ig genes is pre-rearranged in the germline of the cartilaginous fish, making expression possible without rearrangement. To assess whether this allows differential developmental regulation, IgM and IgX heavy chain cDNA sequences from specific tissues and developmental stages have been compared with known germline-joined genomic sequences. Both non-productively rearranged genes and germline-joined genes are transcribed in the embryo and hatchling, but not in the adult.

  18. Pulmonary extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue associated with granulomatous inflammation in a child with chromosome 22q11.2 deletion syndrome (DiGeorge syndrome).

    PubMed

    Pongpruttipan, Tawatchai; Cook, James R; Reyes-Mugica, Miguel; Spahr, Jonathan E; Swerdlow, Steven H

    2012-11-01

    Patients with immunodeficiency disorders have an increased incidence of lymphoproliferative disorders; however, only 4 such patients with DiGeorge/chromosome 22q11.2 deletion syndrome have been reported. We report a case of a pulmonary Epstein-Barr virus-negative extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue in a child with this syndrome.

  19. Detection of Foot-and-mouth Disease Virus RNA and Capsid Protein in Lymphoid Tissues of Convalescent Pigs Does Not Indicate Existence of a Carrier State.

    PubMed

    Stenfeldt, C; Pacheco, J M; Smoliga, G R; Bishop, E; Pauszek, S J; Hartwig, E J; Rodriguez, L L; Arzt, J

    2016-04-01

    A systematic study was performed to investigate the potential of pigs to establish and maintain persistent foot-and-mouth disease virus (FMDV) infection. Infectious virus could not be recovered from sera, oral, nasal or oropharyngeal fluids obtained after resolution of clinical infection with any of five FMDV strains within serotypes A, O and Asia-1. Furthermore, there was no isolation of live virus from tissue samples harvested at 28-100 days post-infection from convalescent pigs recovered from clinical or subclinical FMD. Despite lack of detection of infectious FMDV, there was a high prevalence of FMDV RNA detection in lymph nodes draining lesion sites harvested at 35 days post-infection, with the most frequent detection recorded in popliteal lymph nodes (positive detection in 88% of samples obtained from non-vaccinated pigs). Likewise, at 35 dpi, FMDV capsid antigen was localized within follicles of draining lymph nodes, but without concurrent detection of FMDV non-structural protein. There was a marked decline in the detection of FMDV RNA and antigen in tissue samples by 60 dpi, and no antigen or viral RNA could be detected in samples obtained at 100 dpi. The data presented herein provide the most extensive investigation of FMDV persistence in pigs. The overall conclusion is that domestic pigs are unlikely to be competent long-term carriers of infectious FMDV; however, transient persistence of FMDV protein and RNA in lymphoid tissues is common following clinical or subclinical infection.

  20. The Gut-Associated Lymphoid Tissues in the Small Intestine, Not the Large Intestine, Play a Major Role in Oral Prion Disease Pathogenesis

    PubMed Central

    Donaldson, David S.; Else, Kathryn J.

    2015-01-01

    ABSTRACT Prion diseases are infectious neurodegenerative disorders characterized by accumulations of abnormally folded cellular prion protein in affected tissues. Many natural prion diseases are acquired orally, and following exposure, the early replication of some prion isolates upon follicular dendritic cells (FDC) within gut-associated lymphoid tissues (GALT) is important for the efficient spread of disease to the brain (neuroinvasion). Prion detection within large intestinal GALT biopsy specimens has been used to estimate human and animal disease prevalence. However, the relative contributions of the small and large intestinal GALT to oral prion pathogenesis were unknown. To address this issue, we created mice that specifically lacked FDC-containing GALT only in the small intestine. Our data show that oral prion disease susceptibility was dramatically reduced in mice lacking small intestinal GALT. Although these mice had FDC-containing GALT throughout their large intestines, these tissues were not early sites of prion accumulation or neuroinvasion. We also determined whether pathology specifically within the large intestine might influence prion pathogenesis. Congruent infection with the nematode parasite Trichuris muris in the large intestine around the time of oral prion exposure did not affect disease pathogenesis. Together, these data demonstrate that the small intestinal GALT are the major early sites of prion accumulation and neuroinvasion after oral exposure. This has important implications for our understanding of the factors that influence the risk of infection and the preclinical diagnosis of disease. IMPORTANCE Many natural prion diseases are acquired orally. After exposure, the accumulation of some prion diseases in the gut-associated lymphoid tissues (GALT) is important for efficient spread of disease to the brain. However, the relative contributions of GALT in the small and large intestines to oral prion pathogenesis were unknown. We show that the

  1. Mouse Models for Assessing the Protective Efficacy of Lactobacillus gasseri SBT2055 against Helicobacter suis Infection Associated with the Development of Gastric Mucosa-Associated Lymphoid Tissue Lymphoma.

    PubMed

    Matsui, Hidenori; Takahashi, Tetsufumi; Øverby, Anders; Murayama, Somay Yamagata; Yoshida, Haruno; Yamamoto, Yuji; Nishiyama, Keita; Seto, Yasuyuki; Takahashi, Takashi; Mukai, Takao; Nakamura, Masahiko

    2015-08-01

    Helicobacter suis strain TKY infection has been strongly associated with the development of gastric mucosa-associated lymphoid tissue (MALT) lymphoma in a C57BL/6J mouse model. 1. C57BL/6J mice were intragastrically administered Lactobacillus strains once daily with 10(8)-10(9) colony-forming units (CFU), starting 2 days before intragastric infection with H. suis TKY (approximately 1 × 10(4) copies of 16S rRNA genes) or H. pylori Sydney strain 1 (SS1; 3 × 10(8) CFU) and continuing for 14 days after infection. 2. C57BL/6J mice were given powdered feed mixed with lyophilized L. gasseri SBT2055 (LG2055) cells (5 × 10(8) CFU/g), starting 2 weeks before intragastric infection with H. suis TKY and continuing 12 months after infection. 1. Among the 5 Lactobacillus strains that we examined, only LG2055 exhibited significantly preventive efficacy against both H. suis TKY and H. pylori SS1 at day 15 after infection. 2. Dietary supplementation with LG2055 protected mice from the formation of round protrusive lesions in the gastric fundus 12 months after infection with H. suis TKY, whereas such lesions had developed in the gastric fundus of nonsupplemented mice 12 months after infection. In addition, the formation of lymphoid follicles in gastric mucus layers was suppressed by dietary LG2055 at 3 months after infection. LG2055 administration is effective for suppressing the progression of gastric MALT lymphoma by reducing H. suis colonization. © 2015 John Wiley & Sons Ltd.

  2. Gastrointestinal-associated lymphoid tissue immune reconstitution in a randomized clinical trial of raltegravir versus non-nucleoside reverse transcriptase inhibitor-based regimens.

    PubMed

    Asmuth, David M; Ma, Zhong-Min; Mann, Surinder; Knight, Thomas H; Yotter, Tammy; Albanese, Anthony; Melcher, Gregory P; Troia-Cancio, Paolo; Hayes, Timothy; Miller, Chris J; Pollard, Richard B

    2012-08-24

    To examine immune restoration in duodenal tissue and correlates of reduction of immune activation in chronic HIV-infected patients randomized to different treatment regimens. Randomized clinical trial (RCT) comparing raltegravir to a non-nucleoside reverse transcriptase inhibitor-based regimen, both with fixed-dose tenofovir difumerate/emtricitabine. Antiretroviral therapy (ART)-naive volunteers underwent upper endoscopy for duodenal biopsies before and after 9 months of therapy. Tissue was paraffin-embedded for immunohistochemistry or digested into single-cell suspensions for flow cytometry of lymphocyte subsets and activation phenotype. Plasma-soluble CD14 levels were measured as a surrogate for bacterial translocation. Sixteen HIV-positive and seven control individuals completed study procedures. Small increases in duodenal lamina propria CD4 T-cell numbers were observed, especially when viewed relative to populations in control volunteers, with no differences between treatment arms. The increase in CD4 T-cell percentage was due largely to declines in CD8 T-cell numbers, which were disproportionately increased compared to peripheral blood and controls. Patients randomized to the raltegravir arm had consistent declines in both sCD14 levels and CD8 T-cell numbers in the duodenal tissue lamina propria. This first RCT of lymphocyte population restoration in duodenal tissue demonstrates more modest increases in CD4 T-cell numbers during the first 9 months of therapy than when considering CD3/CD4 percentages only. Although reduced after 9 months of ART, disproportional increased CD8 populations persist in duodenal gastrointestinal-associated lymphoid tissue (GALT). Local rather than systemic antigenic stimulation appears to be driving expanded CD8 T lymphocytes in GALT. Factors other than viral-induced CD8 expansion may be contributing to this local immunologic response. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins

  3. Sinomenine suppresses collagen-induced arthritis by reciprocal modulation of regulatory T cells and Th17 cells in gut-associated lymphoid tissues.

    PubMed

    Tong, Bei; Yu, Juntao; Wang, Ting; Dou, Yannong; Wu, Xin; Kong, Lingyi; Dai, Yue; Xia, Yufeng

    2015-05-01

    Sinomenine (SIN) has long been used as a therapeutic agent of rheumatoid arthritis (RA) in China. However, the discrepancy between low oral bioavailability and higher minimal effective concentration made its action mode mysterious. The present study aimed to gain insight into the mechanisms by which SIN suppressed collagen-induced arthritis (CIA) in rats in view of Th17 and regulatory T (Treg) cell balance. SIN was orally administered, and the clinical symptoms of CIA rats were monitored; inflammatory cytokines levels in serum were measured by ELISA; pharmacokinetic studies were performed in normal and CIA rats; Th17 and Treg cell frequencies were analyzed by flow cytometry. The data showed that SIN treatment resulted in a dramatic decrease of arthritis scores and paw volume of CIA rats, which was accompanied by down-regulation of IL-17A and up-regulation of IL-10 in rat serum. The frequency of Treg cells was increased and the frequency of Th17 cells was decreased in the gut lymphoid tissues of SIN-treated rats. Immunohistochemistry assay demonstrated that more α4β7-positive cells were detained in joint tissues after SIN treatment. Moreover, the anti-arthritis efficacy of SIN disappeared when it was given by intraperitoneal injection, further confirming the action of SIN was gut-dependent. In conclusion, SIN exerts anti-RA action probably through modulating the frequencies of Treg cells and Th17 cells in intestinal lymph nodes and yielding a trafficking of lymphocytes (especially Treg cells) from gut to joint.

  4. Hyaluronan and Hyaluronan-Binding Proteins Accumulate in Both Human Type 1 Diabetic Islets and Lymphoid Tissues and Associate With Inflammatory Cells in Insulitis

    PubMed Central

    Bogdani, Marika; Johnson, Pamela Y.; Potter-Perigo, Susan; Nagy, Nadine; Day, Anthony J.; Bollyky, Paul L.

    2014-01-01

    Hyaluronan (HA) is an extracellular matrix glycosaminoglycan that is present in pancreatic islets, but little is known about its involvement in the development of human type 1 diabetes (T1D). We have evaluated whether pancreatic islets and lymphoid tissues of T1D and nondiabetic organ donors differ in the amount and distribution of HA and HA-binding proteins (hyaladherins), such as inter-α-inhibitor (IαI), versican, and tumor necrosis factor–stimulated gene-6 (TSG-6). HA was dramatically increased both within the islet and outside the islet endocrine cells, juxtaposed to islet microvessels in T1D. In addition, HA was prominent surrounding immune cells in areas of insulitis. IαI and versican were present in HA-rich areas of islets, and both molecules accumulated in diabetic islets and regions exhibiting insulitis. TSG-6 was observed within the islet endocrine cells and in inflammatory infiltrates. These patterns were only observed in tissues from younger donors with disease duration of <10 years. Furthermore, HA and IαI amassed in follicular germinal centers and in T-cell areas in lymph nodes and spleens in T1D patients compared with control subjects. Our observations highlight potential roles for HA and hyaladherins in the pathogenesis of diabetes. PMID:24677718

  5. Mouse Aorta Smooth Muscle Cells Differentiate Into Lymphoid Tissue Organizer-Like Cells on Combined Tumor Necrosis Factor Receptor-1/Lymphotoxin β-Receptor NF-κB Signaling

    PubMed Central

    Lötzer, Katharina; Döpping, Sandra; Connert, Sabine; Gräbner, Rolf; Spanbroek, Rainer; Lemser, Birgit; Beer, Michael; Hildner, Markus; Hehlgans, Thomas; van der Wall, Michael; Mebius, Reina E.; Lovas, Agnes; Randolph, Gwendalyn J.; Weih, Falk; Habenicht, Andreas J.R.

    2010-01-01

    Objective Mouse aorta smooth muscle cells (SMC) express tumor necrosis factor receptor superfamily member 1A (TNFR-1) and lymphotoxin β-receptor (LTβR). Circumstantial evidence has linked the SMC LTβR to tertiary lymphoid organogenesis in hyperlipidemic mice. Here, we explored TNFR-1 and LTβR signaling in cultured SMC. Methods and Results TNFR-1 signaling activated the classical RelA NF-κB pathway, whereas LTβR signaling activated the classical RelA and alternative RelB NF-κB pathways, and both signaling pathways synergized to enhance p100 inhibitor processing to the p52 subunit of NF-κB. Microarrays showed that simultaneous TNFR-1/LTβR activation resulted in elevated mRNA encoding leukocyte homeostatic chemokines CCL2, CCL5, CXCL1, and CX3CL1. Importantly, SMC acquired features of lymphoid tissue organizers, which control tertiary lymphoid organogenesis in autoimmune diseases through hyperinduction of CCL7, CCL9, CXCL13, CCL19, CXCL16, vascular cell adhesion molecule-1, and intercellular adhesion molecule-1. TNFR-1/LTβR cross-talk resulted in augmented secretion of lymphorganogenic chemokine proteins. Supernatants of TNFR-1/LTβR–activated SMC markedly supported migration of splenic T cells, B cells, and macrophages/dendritic cells. Experiments with ltbr−/− SMC indicated that LTβR-RelB activation was obligatory to generate the lymphoid tissue organizer phenotype. Conclusion SMC may participate in the formation of tertiary lymphoid tissue in atherosclerosis by upregulation of lymphorganogenic chemokines involved in T-lymphocyte, B-lymphocyte, and macrophage/dendritic cell attraction. PMID:20139367

  6. Acute infection with bovine viral diarrhea virus of low or high virulence leads to depletion and redistribution of WC1(+) γδ T cells in lymphoid tissues of beef calves.

    PubMed

    Palomares, Roberto A; Sakamoto, Kaori; Walz, Heather L; Brock, Kenny V; Hurley, David J

    2015-10-15

    The objective of this study was to determine the abundance and distribution of γδ T lymphocytes in lymphoid tissue during acute infection with high (HV) or low virulence (LV) non-cytopathic bovine viral diarrhea virus (BVDV) in beef calves. This study was performed using tissue samples from a previous experiment in which thirty beef calves were randomly assigned to 1 of 3 groups: LV [n=10; animals inoculated intranasally (IN) with LV BVDV-1a (strain SD-1)], HV [n=10; animals inoculated IN with HV BVDV-2 (strain 1373)], and control (n=10; animals inoculated with cell culture medium). On day 5 post inoculation, animals were euthanized, and samples from spleen and mesenteric lymph nodes (MLN) were collected to assess the abundance of WC1(+) γδ T cells. A higher proportion of calves challenged with BVDV showed signs of apoptosis and cytophagy in MLN and spleen samples compared to the control group. A significantly lower number of γδ T cells was observed in spleen and MLN from calves in HV and LV groups than in the control calves (P<0.05). In conclusion, acute infection with HV or LV BVDV resulted in depletion of WC1(+) γδ T cells in mucosal and systemic lymphoid tissues at five days after challenge in beef calves. This reduction in γδ T cells in the studied lymphoid tissues could be also due to lymphocyte trafficking to other tissues.

  7. Lack of prion accumulation in lymphoid tissues of PRNP ARQ/ARR sheep intracranially inoculated with the agent of scrapie

    USDA-ARS?s Scientific Manuscript database

    Sheep scrapie is a transmissible spongiform encephalopathy that can be transmitted horizontally. The prion protein gene (PRNP) profoundly influences the susceptibility of sheep to the scrapie agent and the tissue levels and distribution of PrPSc in affected sheep. The purpose of this study was to co...

  8. Exploring the Feasibility of Multi-Site Flow Cytometric Processing of Gut Associated Lymphoid Tissue with Centralized Data Analysis for Multi-Site Clinical Trials

    PubMed Central

    McGowan, Ian; Anton, Peter A.; Elliott, Julie; Cranston, Ross D.; Duffill, Kathryn; Althouse, Andrew D.; Hawkins, Kevin L.; De Rosa, Stephen C.

    2015-01-01

    The purpose of this study was to determine whether the development of a standardized approach to the collection of intestinal tissue from healthy volunteers, isolation of gut associated lymphoid tissue mucosal mononuclear cells (MMC), and characterization of mucosal T cell phenotypes by flow cytometry was sufficient to minimize differences in the normative ranges of flow parameters generated at two trial sites. Forty healthy male study participants were enrolled in Pittsburgh and Los Angeles. MMC were isolated from rectal biopsies using the same biopsy acquisition and enzymatic digestion protocols. As an additional comparator, peripheral blood mononuclear cells (PBMC) were collected from the study participants. For quality control, cryopreserved PBMC from a single donor were supplied to both sites from a central repository (qPBMC). Using a jointly optimized standard operating procedure, cells were isolated from tissue and blood and stained with monoclonal antibodies targeted to T cell phenotypic markers. Site-specific flow data were analyzed by an independent center which analyzed all data from both sites. Ranges for frequencies for overall CD4+ and CD8+ T cells, derived from the qPBMC samples, were equivalent at both UCLA and MWRI. However, there were significant differences across sites for the majority of T cell activation and memory subsets in qPBMC as well as PBMC and MMC. Standardized protocols to collect, stain, and analyze MMC and PBMC, including centralized analysis, can reduce but not exclude variability in reporting flow data within multi-site studies. Based on these data, centralized processing, flow cytometry, and analysis of samples may provide more robust data across multi-site studies. Centralized processing requires either shipping of fresh samples or cryopreservation and the decision to perform centralized versus site processing needs to take into account the drawbacks and restrictions associated with each method. PMID:26010577

  9. Light and electron microscopic study of the eyelids, conjunctiva-associated lymphoid tissue and lacrimal gland in Bilgorajska Goose (Anser anser).

    PubMed

    Klećkowska-Nawrot, Joanna; Nowaczyk, Renata; Goździewska-Harłajczuk, Karolina; Barszcz, Karolina; Kowalczyk, Artur; Łukaszewicz, Ewa

    2016-01-01

    Normal structure of the accessory organs of the eye is essential for normal eye physiology. Among the most important accessory organs of the eye are the eyelids, the conjunctiva-associated lymphoid tissue (CALT) and the lacrimal gland (LG). The aim of this study was to demonstrate the histological structure of the eyelids and LG by histochemical and ultrastructural analysis. The study was performed on 13 adult female Bilgorajska geese. Eyelid samples were stained with the Alcian blue (AB pH 2.5) and periodic acid-Schiff (PAS) methods. Staining methods used for LG were AB pH 2.5, aldehyde fuchsin (AF), PAS and Hale's dialysed iron (HDI). Within the connective tissue of the eyelids, well-developed, diffuse, CALT follicles were observed, mostly under the conjunctival epithelium. Numerous lymphocytes were present within loose connective tissue. Staining of the eyelids with the PAS method demonstrated the presence of goblet cells of a mucous nature, and AB pH 2.5 staining indicated the presence of sulfated acid mucopolysaccharides. PAS staining of LG revealed the presence of secretory cells containing weakly PAS-positive granules. All epithelial cells of the corpus glandulae and the duct systems reacted positively to AB pH 2.5. HDI staining detected the presence of carboxylated acid mucopolysaccharides. Transmission electron microscopy investigations revealed two types of secretory epithelial cells in LG. Both types of LG cells contained drop-like secretory vesicles of different sizes with low or high electron density in cytoplasm, as well as small and large lipid vacuoles, and numerous small primary lysosomes.

  10. Marginal zone lymphoma of mucosa-associated lymphoid tissue with prominent plasma cell differentiation affecting the palatine tonsil: histopathological and immunohistochemical analysis.

    PubMed

    Carlos Bregni, Román; Nuyens, Michel; Vassallo, José; Soares, Fernando Augusto; Romañach, Mário José; León, Jorge Esquiche; Almeida, Oslei Paes

    2012-04-01

    Non-Hodgkin lymphomas (NHLs) of the oral cavity and oropharynx constitute 13% of all primary extranodal NHLs. Marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT lymphoma) in the palatine tonsil is rare, corresponding to 6% of the NHLs of the Waldeyer ring. Some cases of MALT lymphoma can present prominent plasma cell differentiation, and less commonly, monoclonal gammopathy. The differential diagnosis of these cases from other NHLs with plasmacytic differentiation or plasma cell neoplasms is very difficult. In this article, we describe a rare case of MALT lymphoma in a 34-year-old man presenting as a swelling of the palatine tonsil. The tumor mass was diagnosed as MALT lymphoma with prominent plasma cell differentiation. Systemic evaluation was noncontributory. This is the first report of MALT lymphoma showing extensive plasmacytic differentiation of the palatine tonsil, and reinforces a possible relationship between extramedullary plasmacytoma and MALT lymphoma. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. A Multicenter Phase II Study of Local Radiation Therapy for Stage IEA Mucosa-Associated Lymphoid Tissue Lymphomas: A Preliminary Report From the Japan Radiation Oncology Group (JAROG)

    SciTech Connect

    Isobe, Koichi Kagami, Yoshikazu; Higuchi, Keiko; Kodaira, Takeshi; Hasegawa, Masatoshi; Shikama, Naoto; Nakazawa, Masanori; Fukuda, Ichiro; Nihei, Keiji; Ito, Kana; Teshima, Teruki; Matsuno, Yoshihiro; Oguchi, Masahiko

    2007-11-15

    Purpose: The aim of this study was to evaluate the efficacy and toxicity of moderate dose radiation therapy (RT) for mucosa-associated lymphoid tissue (MALT) lymphoma in a prospective multicenter phase II trial. Methods and Materials: The subjects in this study were 37 patients with MALT lymphoma between April 2002 and November 2004. There were 16 male and 21 female patients, ranging in age from 24 to 82 years, with a median of 56 years. The primary tumor originated in the orbit in 24 patients, in the thyroid and salivary gland in 4 patients each, and 5 in the others. The median tumor dose was 30.6 Gy (range, 30.6-39.6 Gy), depending on the primary site and maximal tumor diameter. The median follow-up was 37.3 months. Results: Complete remission (CR) or CR/unconfirmed was achieved in 34 patients (92%). The 3-year overall survival, progression-free survival, and local control probability were 100%, 91.9%, and 97.3%, respectively. Thirteen patients experienced Grade 1 acute toxicities including dermatitis, mucositis, and conjunctivitis. One patient developed Grade 2 taste loss. Regarding late toxicities, Grade 2 reactions including hypothyroidism, and radiation pneumonitis were observed in three patients, and Grade 3 cataract was seen in three patients. Conclusions: This prospective phase II study demonstrated that moderate dose RT was highly effective in achieving local control with acceptable morbidity in 37 patients with MALT lymphoma.

  12. Low-Dose Radiation Treatment in Pulmonary Mucosa-Associated Lymphoid Tissue Lymphoma: A Plausible Approach? A Single-Institution Experience in 10 Patients

    SciTech Connect

    Girinsky, Theodore; Paumier, Amaury; Ferme, Christophe; Hanna, Colette; Ribrag, Vincent; Leroy-Ladurie, Francois; Ghalibafian, Mithra

    2012-07-01

    Purpose: To propose an alternative approach for treatment of pulmonary marginal zone lymphoma, using a very small radiation dose (2 Multiplication-Sign 2 Gy) delivered exclusively to tumor sites. Methods and Materials: Patients had localized pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma according to the World Health Organization classification. The 6-MV radiation treatments were delivered using tumor-limited fields, except in cases of diffuse bilateral involvement. Two daily fractions of 2 Gy were delivered to tumor-limited fields using a 6-MV linear accelerator. Results: Ten patients with pulmonary MALT lymphoma entered the study. All but 1 had localized tumor masses. The median follow-up was 56 months (range, 2-103 months). Complete remission or an unconfirmed complete remission was obtained in 60% of patients within the first 2 months, and two additional partial responses were converted into a long-term unconfirmed complete remission. All patients are well and alive, no local progression was observed, and the 5-year progression-free survival rate was 87.5% (95% confidence interval 49%-97%). Conclusions: Our results suggest that extremely low radiation doses delivered exclusively to tumor sites might be a treatment option in pulmonary MALT lymphoma.

  13. Stage 3 immature human natural killer cells found in secondary lymphoid tissue constitutively and selectively express the TH17 cytokine interleukin-22

    PubMed Central

    Hughes, Tiffany; Becknell, Brian; McClory, Susan; Briercheck, Edward; Freud, Aharon G.; Zhang, Xiaoli; Mao, Hsiaoyin; Nuovo, Gerard; Yu, Jianhua

    2009-01-01

    Considerable functional heterogeneity within human natural killer (NK) cells has been revealed through the characterization of distinct NK-cell subsets. Accordingly, a small subset of CD56+NKp44+NK cells, termed NK-22 cells, was recently described within secondary lymphoid tissue (SLT) as IL-22− when resting, with a minor fraction of this population becoming IL-22+ when activated. Here we discover that the vast majority of stage 3 immature NK (iNK) cells in SLT constitutively and selectively express IL-22, a TH17 cytokine important for mucosal immunity, whereas earlier and later stages of NK developmental intermediates do not express IL-22. These iNK cells have a surface phenotype of CD34−CD117+CD161+CD94−, largely lack expression of NKp44 and CD56, and do not produce IFN-γ or possess cytolytic activity. In summary, stage 3 iNK cells are highly enriched for IL-22 and IL-26 messenger RNA, and IL-22 protein production, but do not express IL-17A or IL-17F. PMID:19244159

  14. Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue type arising in the pleura with pleural fibrous plaques in a lathe worker.

    PubMed

    Nakatsuka, Shin-ichi; Nagano, Teruaki; Kimura, Hayato; Hanada, Shoji; Inoue, Hidetoshi; Iwata, Takashi

    2012-06-01

    Our patient was an 86-year-old man who had worked as a lathe operator for 40 years. He had no history of tuberculosis, pyothorax, or autoimmune disease. He had not been exposed to asbestos. He was asymptomatic, but an imaging study showed gradually increasing pleural plaques. A biopsy specimen of a pleural lesion showed sclerosis of the pleura and diffuse infiltration of small- to medium-sized B lymphocytes. Polymerase chain reaction-based analysis detected monoclonal rearrangement of immunoglobulin heavy-chain genes. Histologic diagnosis was extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue type (MALT lymphoma). The lymphoma was negative for Epstein-Barr virus. We report a rare case of a metal worker with MALT lymphoma arising in the pleura with pleural fibrous plaques. It is speculated that MALT lymphoma might develop in the background of pneumoconiosis. Inflammatory and/or immunologic reactions to metal particles might contribute to the oncogenesis of this tumor. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. Early, Isolated Duodenal Mucosa-Associated Lymphoid Tissue Lymphoma Presenting without Symptoms or Grossly Apparent Endoscopic Lesions and Diagnosed by Random Duodenal Biopsies

    PubMed Central

    Gjeorgjievski, Mihajlo; Makki, Issa; Khanal, Pradeep; Amin, Mitual B.; Blenc, Ann Marie; Desai, Tusar; Cappell, Mitchell S.

    2016-01-01

    Clinical data regarding mucosa-associated lymphoid tissue lymphoma (MALToma) solely involving the duodenum are sparse because of the relative rarity of the disease. A comprehensive literature review revealed only 17 cases reported until 2004, and only a moderate number of cases have been reported since. MALToma can be asymptomatic in its very early stages but frequently produces localized or nonspecific symptoms, including early satiety, abdominal pain, vomiting, and involuntary weight loss in later stages. While gastric MALToma is strongly associated with gastric Helicobactor pylori infection, duodenal MALToma is often unassociated with H. pylori infection. A 74-year-old female presented with only dysphagia (without symptoms referable to a duodenal lesion), without systemic ‘B’ symptoms, and with no evident duodenal lesions at esophagogastroduodenoscopy; however, she was diagnosed with duodenal MALToma by pathologic examination of random duodenal biopsies performed to exclude celiac disease. An important clinical feature of this case is that duodenal MALToma was diagnosed by pathologic analysis of duodenal biopsies despite (1) no endoscopically apparent duodenal lesions; (2) duodenal involvement without gastric involvement; (3) lack of symptoms attributable to duodenal MALToma, and (4) absence of evident H. pylori infection. This work shows that early duodenal MALToma can be difficult to diagnose because of absent symptoms, absence of gastric involvement, absence of endoscopic abnormalities, and absence of H. pylori infection; it may require random duodenal biopsies for diagnosis. PMID:27482191

  16. Chronic Stress Induces Structural Alterations in Splenic Lymphoid Tissue That Are Associated with Changes in Corticosterone Levels in Wistar-Kyoto Rats

    PubMed Central

    Hernandez, María Eugenia; Martinez-Mota, Lucia; Salinas, Citlaltepetl; Marquez-Velasco, Ricardo; Hernandez-Chan, Nancy G.; Morales-Montor, Jorge; Pérez-Tapia, Mayra; Streber, María L.; Granados-Camacho, Ivonne; Becerril, Enrique; Javier, Baquera-Heredia; Pavón, Lenin

    2013-01-01

    Major depressive disorder patients present chronic stress and decreased immunity. The Wistar-Kyoto rat (WKY) is a strain in which the hypothalamic-pituitary-adrenal axis is overactivated. To determine whether chronic stress induces changes in corticosterone levels and splenic lymphoid tissue, 9-week-old male rats were subject to restraint stress (3 h daily), chemical stress (hydrocortisone treatment, 50 mg/Kg weight), mixed stress (restraint plus hydrocortisone), or control treatment (without stress) for 1, 4, and 7 weeks. The serum corticosterone levels by RIA and spleens morphology were analyzed. Corticosterone levels as did the structure, size of the follicles and morphology of the parenchyma (increase in red pulp) in the spleen, varied depending on time and type of stressor. These changes indicate that chronic stress alters the immune response in the spleen in WKY rats by inducing morphological changes, explaining in part the impaired immunity that develops in organisms that are exposed to chronic stress. PMID:23533999

  17. Evolutionarily Conserved TCR Binding Sites, Identification of T Cells in Primary Lymphoid Tissues, and Surprising Trans-Rearrangements in Nurse Shark

    PubMed Central

    Criscitiello, Michael F.; Ohta, Yuko; Saltis, Mark; McKinney, E. Churchill; Flajnik, Martin F.

    2011-01-01

    Cartilaginous fish are the oldest animals that generate RAG-based Ag receptor diversity. We have analyzed the genes and expressed transcripts of the four TCR chains for the first time in a cartilaginous fish, the nurse shark (Ginglymostoma cirratum). Northern blotting found TCR mRNA expression predominantly in lymphoid and mucosal tissues. Southern blotting suggested translocon-type loci encoding all four chains. Based on diversity of V and J segments, the expressed combinatorial diversity for γ is similar to that of human, α and β may be slightly lower, and δ diversity is the highest of any organism studied to date. Nurse shark TCRδ have long CDR3 loops compared with the other three chains, creating binding site topologies comparable to those of mammalian TCR in basic paratope structure; additionally, nurse shark TCRδ CDR3 are more similar to IgH CDR3 in length and heterogeneity than to other TCR chains. Most interestingly, several cDNAs were isolated that contained IgM or IgW V segments rearranged to other gene segments of TCRδ and α. Finally, in situ hybridization experiments demonstrate a conservation of both α/β and γ/δ T cell localization in the thymus across 450 million years of vertebrate evolution, with γ/δ TCR expression especially high in the subcapsular region. Collectively, these data make the first cellular identification of TCR-expressing lymphocytes in a cartilaginous fish. PMID:20488795

  18. Evolutionarily conserved TCR binding sites, identification of T cells in primary lymphoid tissues, and surprising trans-rearrangements in nurse shark.

    PubMed

    Criscitiello, Michael F; Ohta, Yuko; Saltis, Mark; McKinney, E Churchill; Flajnik, Martin F

    2010-06-15

    Cartilaginous fish are the oldest animals that generate RAG-based Ag receptor diversity. We have analyzed the genes and expressed transcripts of the four TCR chains for the first time in a cartilaginous fish, the nurse shark (Ginglymostoma cirratum). Northern blotting found TCR mRNA expression predominantly in lymphoid and mucosal tissues. Southern blotting suggested translocon-type loci encoding all four chains. Based on diversity of V and J segments, the expressed combinatorial diversity for gamma is similar to that of human, alpha and beta may be slightly lower, and delta diversity is the highest of any organism studied to date. Nurse shark TCRdelta have long CDR3 loops compared with the other three chains, creating binding site topologies comparable to those of mammalian TCR in basic paratope structure; additionally, nurse shark TCRdelta CDR3 are more similar to IgH CDR3 in length and heterogeneity than to other TCR chains. Most interestingly, several cDNAs were isolated that contained IgM or IgW V segments rearranged to other gene segments of TCRdelta and alpha. Finally, in situ hybridization experiments demonstrate a conservation of both alpha/beta and gamma/delta T cell localization in the thymus across 450 million years of vertebrate evolution, with gamma/delta TCR expression especially high in the subcapsular region. Collectively, these data make the first cellular identification of TCR-expressing lymphocytes in a cartilaginous fish.

  19. Which test to use to detect Helicobacter pylori infection in patients with low-grade gastric mucosa-associated lymphoid tissue lymphoma?

    PubMed

    Lehours, Philippe; Ruskone-Fourmestraux, Agnès; Lavergne, Anne; Cantet, Franck; Mégraud, Francis

    2003-02-01

    Helicobacter pylori is involved in the pathogenesis of lymphoma of the gastric mucosa-associated lymphoid tissue (MALT). Because gastric MALT lymphoma is a rare disease, few studies comparing the accuracy of diagnostic tests in this group of patients have been carried out, and only a limited number of tests (essentially histological) were performed. The aim of our study was to compare the results of four different diagnostic methods used to detect H. pylori (histology, culture, polymerase chain reaction, and serology) in a prospective multicenter study. A patient was considered to be H. pylori positive if culture or histology was positive. During the period 1995-2000, a total of 90 patients with low-grade gastric MALT lymphoma were enrolled. Results for the four tests were available for 56 patients (62.2%). Among these patients, the four tests were concordant in 35 cases (62.5%), i.e., were positive in 19 cases (33.9%) and negative in 16 patients (17.8%). Histology (39/40 positive, 97.5%) and serology (38/40 positive, 95.0%) were the most sensitive tests. Polymerase chain reaction (PCR) and culture were positive in 52.5% and 50%, respectively. The cagA gene was detected in 47.4% of the strains.

  20. Helicobacter pylori Eradication Therapy Is Effective as the Initial Treatment for Patients with H. pylori-Negative and Disseminated Gastric Mucosa-Associated Lymphoid Tissue Lymphoma

    PubMed Central

    Gong, Eun Jeong; Ahn, Ji Yong; Jung, Hwoon-Yong; Park, Hyungchul; Ko, Young Bo; Na, Hee Kyong; Jung, Kee Wook; Kim, Do Hoon; Lee, Jeong Hoon; Choi, Kee Don; Song, Ho June; Lee, Gin Hyug; Kim, Jin-Ho

    2016-01-01

    Background/Aims We investigated the effectiveness of Helicobacter pylori eradication therapy for gastric mucosa-associated lymphoid tissue (MALT) lymphoma regardless of the H. pylori infection status or disease stage. Methods From November 1995 to September 2014, 345 subjects who were diagnosed with gastric MALT lymphoma and had received eradication therapy as their first-line treatment were eligible for inclusion in this study. A retrospective review was performed using the medical records. Results Of the 345 patients, H. pylori infection was detected in 317 patients (91.9%). The complete remission (CR) rate after eradication therapy was 82.3%, which was higher in H. pylori-positive patients than in H. pylori-negative patients (84.5% vs 57.1%, p=0.001). CR rates after eradication did not present significant differences between stages, and the CR rate was 83.3% for stage IE1 and 74.4% for stage IE2 or above (p=0.167). The overall CR rate was 87.2% after additional treatment, and neither H. pylori infection status nor stage showed differences according to the treatment response. Conclusions Eradication therapy led to CR in 57.1% of H. pylori-negative patients and in 74.4% of patients with stage IE2 or above. Eradication therapy is worthwhile as an initial treatment for gastric MALT lymphoma regardless of the H. pylori infection status and stage. PMID:27114423

  1. Pathologic findings in adenosine deaminase deficient-severe combined immunodeficiency. II. Thymus, spleen, lymph node, and gastrointestinal tract lymphoid tissue alterations.

    PubMed Central

    Ratech, H.; Hirschhorn, R.; Greco, M. A.

    1989-01-01

    Eight autopsies of patients with adenosine deaminase deficient-severe combined immunodeficiency disease (ADA-SCID) were reviewed with special emphasis on the lymphoid tissues. The thymus histology in five cases was remarkably uniform, whether or not prior ADA enzyme replacement or immunologic reconstitution therapy had been administered. Lymph nodes and spleens in all cases examined showed a residual nonlymphoid architectural framework corresponding to usual T and B cell zones found in normals. The development of an extranodal, monoclonal IgA lambda B cell immunoblastic lymphoma as a terminal event in one patient after several years of successful ADA enzyme replacement therapy through multiple red blood cell transfusions is described. In another patient with long-term ADA enzyme replacement, a terminal autoimmune hemolytic anemia developed. Autopsy revealed severe deposits of iron in the B cell zones of the lymph nodes, which is an unusual location. In addition, iron deposits outlined the splenic trabeculae, as well as the ring fibers and bridging fibers of the splenic sinuses. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 PMID:2596574

  2. Analysis of Th17 and Tc17 Frequencies and Antiviral Defenses in Gut-Associated Lymphoid Tissue of Chronic HIV-1 Positive Patients

    PubMed Central

    d'Ettorre, Gabriella; Ceccarelli, Giancarlo; Andreotti, Mauro; Selvaggi, Carla; Giustini, Noemi; Serafino, Sara; Schietroma, Ivan; Nunnari, Giuseppe; Antonelli, Guido; Vullo, Vincenzo; Scagnolari, Carolina

    2015-01-01

    The complex relationship between both the Th1/Th17 and Tc1/Tc17 axis and innate defences in the intestinal mucosa during HIV-1 infection has not been well characterized. This study examined the frequency, phenotype, and functional status of T cell populations in the gut-associated lymphoid tissue and peripheral blood of virologically suppressed HIV-1-infected patients on therapy, focusing on the Th1, Th17, Tc1, and Tc17 cell subsets. We found a persistent immune cell activation (CD38 and HLADR expression) into the GALT despite the higher levels of Th17 and Tc17 in respect to peripheral blood. An upregulation of type I IFN response in GALT compared to the peripheral blood compartment was also recorded. Furthermore, IFN-α/β levels were negatively related to the frequencies of Th1 naïve cells and Tc1 cell subsets (naïve, central memory, and effector memory) in the GALT. In contrast, no relationships between type I IFN response and Th1 or Tc1 cell subsets in peripheral blood compartment and between IFN-α/β and Th17/Tc17 in both GALT and peripheral blood district were recorded. These data indicate that prolonged antiretroviral treatment improves GALT immune function despite the persistence of immune activation and type I IFN response in chronic HIV-1 positive patients. PMID:26221062

  3. Spontaneous regression of primary extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) colliding with invasive ductal carcinoma of the breast: a case report

    PubMed Central

    Matsuda, Ikuo; Watanabe, Takahiro; Enomoto, Yukie; Takatsuka, Yuichi; Miyoshi, Yasuo; Hirota, Seiichi

    2014-01-01

    Malignant lymphomas of the breast, whether they are primary or secondary, are rare diseases, constituting only around 0.1 to 0.15% of the primary neoplasm of the breast. Although the most prevalent histological subtype is diffuse large B-cell lymphoma, primary extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) also occurs in the breast as in other extranodal sites, comprising about 15% of malignant lymphomas of the breast. In many cases, primary MALT lymphoma of the breast is low grade lymphoma, localized in the breast with indolent behavior and good prognosis. Here we report a case of spontaneous regression of primary MALT lymphoma of the breast. The lymphoma collided with invasive ductal carcinoma in the breast. Both tumors were identified in the Vacora biopsy specimen before the operation. However, the lymphoma disappeared, while the carcinoma remained, in the resected mass. To our knowledge, this is the first case report of spontaneous regression of MALT lymphoma of the breast colliding with breast cancer. PMID:25400790

  4. Limited role of bone marrow aspiration and biopsy in the initial staging work-up of gastric mucosa-associated lymphoid tissue lymphoma in Korea.

    PubMed

    Min, Byung-Hoon; Park, Jun Young; Kim, Eun Ran; Min, Yang Won; Lee, Jun Haeng; Rhee, Poong-Lyul; Rhee, Jong Chul; Kim, Jae J

    2014-11-01

    The aim of this study was to investigate the frequency of disseminated gastric mucosa-associated lymphoid tissue (MALT) lymphoma and the role of bone marrow study in the initial staging work-up. A total of 194 patients with gastric MALT lymphoma was enrolled. The incidence of disseminated disease was evaluated in the initial staging work-up. The demographic data and tumor characteristics were compared according to Helicobacter pylori infection status. Localized disease of Lugano stage I accounted for 97.4% of the enrolled cases. Abdominal computed tomography revealed abdominal lymph node metastasis in five patients (2.6%). Bone marrow (BM) involvement was found in only one patient without H. pylori infection (0.5%). No patient showed positive findings on chest computed tomography or positron emission tomography. H. pylori-negative cases showed a significantly higher frequency of advanced-stage disease than H. pylori-positive cases (10.0% vs 0.6%). In patients achieving complete remission, no extragastric recurrence occurred during follow-up. The incidence of disseminated disease, including BM involvement, was very low in Korean gastric MALT lymphoma patients. It might be beneficial to perform BM aspiration and biopsy as a part of staging work-up only in patients with risk factors for advanced disease such as H. pylori negativity.

  5. Analysis of multiply spliced transcripts in lymphoid tissue reservoirs of rhesus macaques infected with RT-SHIV during HAART.

    PubMed

    Deere, Jesse D; Kauffman, Robert C; Cannavo, Elda; Higgins, Joanne; Villalobos, Andradi; Adamson, Lourdes; Schinazi, Raymond F; Luciw, Paul A; North, Thomas W

    2014-01-01

    Highly active antiretroviral therapy (HAART) can reduce levels of human immunodeficiency virus type 1 (HIV-1) to undetectable levels in infected individuals, but the virus is not eradicated. The mechanisms of viral persistence during HAART are poorly defined, but some reservoirs have been identified, such as latently infected resting memory CD4⁺ T cells. During latency, in addition to blocks at the initiation and elongation steps of viral transcription, there is a block in the export of viral RNA (vRNA), leading to the accumulation of multiply-spliced transcripts in the nucleus. Two of the genes encoded by the multiply-spliced transcripts are Tat and Rev, which are essential early in the viral replication cycle and might indicate the state of infection in a given population of cells. Here, the levels of multiply-spliced transcripts were compared to the levels of gag-containing RNA in tissue samples from RT-SHIV-infected rhesus macaques treated with HAART. Splice site sequence variation was identified during development of a TaqMan PCR assay. Multiply-spliced transcripts were detected in gastrointestinal and lymphatic tissues, but not the thymus. Levels of multiply-spliced transcripts were lower than levels of gag RNA, and both correlated with plasma virus loads. The ratio of multiply-spliced to gag RNA was greatest in the gastrointestinal samples from macaques with plasma virus loads <50 vRNA copies per mL at necropsy. Levels of gag RNA and multiply-spliced mRNA in tissues from RT-SHIV-infected macaques correlate with plasma virus load.

  6. Analysis of Multiply Spliced Transcripts in Lymphoid Tissue Reservoirs of Rhesus Macaques Infected with RT-SHIV during HAART

    PubMed Central

    Deere, Jesse D.; Kauffman, Robert C.; Cannavo, Elda; Higgins, Joanne; Villalobos, Andradi; Adamson, Lourdes; Schinazi, Raymond F.; Luciw, Paul A.; North, Thomas W.

    2014-01-01

    Highly active antiretroviral therapy (HAART) can reduce levels of human immunodeficiency virus type 1 (HIV-1) to undetectable levels in infected individuals, but the virus is not eradicated. The mechanisms of viral persistence during HAART are poorly defined, but some reservoirs have been identified, such as latently infected resting memory CD4+ T cells. During latency, in addition to blocks at the initiation and elongation steps of viral transcription, there is a block in the export of viral RNA (vRNA), leading to the accumulation of multiply-spliced transcripts in the nucleus. Two of the genes encoded by the multiply-spliced transcripts are Tat and Rev, which are essential early in the viral replication cycle and might indicate the state of infection in a given population of cells. Here, the levels of multiply-spliced transcripts were compared to the levels of gag-containing RNA in tissue samples from RT-SHIV-infected rhesus macaques treated with HAART. Splice site sequence variation was identified during development of a TaqMan PCR assay. Multiply-spliced transcripts were detected in gastrointestinal and lymphatic tissues, but not the thymus. Levels of multiply-spliced transcripts were lower than levels of gag RNA, and both correlated with plasma virus loads. The ratio of multiply-spliced to gag RNA was greatest in the gastrointestinal samples from macaques with plasma virus loads <50 vRNA copies per mL at necropsy. Levels of gag RNA and multiply-spliced mRNA in tissues from RT-SHIV-infected macaques correlate with plasma virus load. PMID:24505331

  7. Seeded amplification of chronic wasting disease prions in nasal brushings and recto-anal mucosal associated lymphoid tissues from elk by real time quaking-induced conversion

    USGS Publications Warehouse

    Haley, Nicholas J.; Siepker, Chris; Hoon-Hanks , Laura L.; Mitchell, Gordon; Walter, William D.; Manca, Matteo; Monello, Ryan J.; Powers, Jenny G.; Wild, Margaret A.; Hoover, Edward A.; Caughey, Byron; Richt, Jürgen a.; Fenwick, B.W.

    2016-01-01

    Chronic wasting disease (CWD), a transmissible spongiform encephalopathy of cervids, was first documented nearly 50 years ago in Colorado and Wyoming and has since been detected across North America and the Republic of Korea. The expansion of this disease makes the development of sensitive diagnostic assays and antemortem sampling techniques crucial for the mitigation of its spread; this is especially true in cases of relocation/reintroduction or prevalence studies of large or protected herds, where depopulation may be contraindicated. This study evaluated the sensitivity of the real-time quaking-induced conversion (RT-QuIC) assay of recto-anal mucosa-associated lymphoid tissue (RAMALT) biopsy specimens and nasal brushings collected antemortem. These findings were compared to results of immunohistochemistry (IHC) analysis of ante- and postmortem samples. RAMALT samples were collected from populations of farmed and free-ranging Rocky Mountain elk (Cervus elaphus nelsoni; n = 323), and nasal brush samples were collected from a subpopulation of these animals (n = 205). We hypothesized that the sensitivity of RT-QuIC would be comparable to that of IHC analysis of RAMALT and would correspond to that of IHC analysis of postmortem tissues. We found RAMALT sensitivity (77.3%) to be highly correlative between RT-QuIC and IHC analysis. Sensitivity was lower when testing nasal brushings (34%), though both RAMALT and nasal brush test sensitivities were dependent on both the PRNP genotype and disease progression determined by the obex score. These data suggest that RT-QuIC, like IHC analysis, is a relatively sensitive assay for detection of CWD prions in RAMALT biopsy specimens and, with further investigation, has potential for large-scale and rapid automated testing of antemortem samples for CWD.

  8. Immunoglobulin and specific-antibody synthesis in vitro by enteral and nonenteral lymphoid tissues after subcutaneous cholera immunization.

    PubMed Central

    Svennerholm, A M; Holmgren, J

    1977-01-01

    An in vitro culture technique with synthesis of 14C-labeled protein has been used to study immunoglobulin and specific-antibody formation by spleen, mesenteric lymph nodes, Peyer's patches, and small intestine of rabbits, which were immunized twice subcutaneously with Vibrio cholerae lipopolysaccharide (LPS) and enterotoxin; saline-injected rabbits served as controls. Newly synthesized immunoglobulin G (IgG), IgA, and IgM were quantitated by liquid scintillation after their isolation by means of affinity chromatography from columns with immunoglobulin class-specific antibodies coupled to Sepharose. Specific antibodies were similarly measured after purification from gels derivatized with LPS or cholera toxin. The isolated antibodies had full biological activity as studied in protection tests. The immunization increased the overall IgM synthesis in the spleen. It also enhanced the production of IgA and IgG in Peyer's patches and of IgA in intestine. Significant synthesis of radiolabeled antibodies against both V. cholerae LPS and enterotoxin was found in spleen as well as in Peyer's patches of immunized animals. Titration with an enzyme-linked immunosorbent assay (ELISA) showed significant levels of IgG as well as IgA antibodies in incubation medium from all the studied tissues, whereas specific IgM was only found for spleen and mesenteric lymph nodes. Simultaneous tissue incubations at 37 degrees C and in an ice bath indicated that the major part of the antibodies registered with the ELISA represented de novo synthesis. PMID:844901

  9. The effect of continuous low dose-rate gamma irradiation on cell population kinetics of lymphoid tissue

    NASA Technical Reports Server (NTRS)

    Foster, B. R.

    1974-01-01

    Cellular response and cell population kinetics were studied during lymphopoiesis in the thymus of the mouse under continuous gamma irradiation using autoradiographic techniques and specific labeling with tritiated thymidine. On the basis of tissue weights, it is concluded that the response of both the thymus and spleen to continuous low dose-rate irradiation is multiphasic. That is, alternating periods of steady state growth, followed by collapse, which in turn is followed by another period of homeostasis. Since there are two populations of lymphocytes - short lived and long-lived, it may be that different phases of steady state growth are mediated by different lymphocytes. The spleen is affected to a greater extent with shorter periods of steady-state growth than exhibited by the thymus.

  10. Human lymphocyte subpopulations. Human thymus-lymphoid tissue (HTL) antigen-positive lymphocytes forming rosettes with sheep erythrocytes and HTL antigen-negative lymphocytes interacting with antigen-antibody-complement complexes

    PubMed Central

    Yata, J.; Tsukimoto, I.; Tachibana, T.

    1973-01-01

    Human lymphocytes from various lymphoid tissues were studied for the relationship between the existence of HTL (human thymus-lymphoid tissue) antigen, and binding of sheep erythrocytes (E) or sheep erythrocyte–antibody-complement complexes (EA(IgM)C43). E adhered to the majority of thymus lymphocytes and formed rosettes. These lymphocytes were shown to be HTL antigen positive by immunofluorescence performed simultaneously. In the peripheral lymphoid tissues, 10–30% of lymphocytes formed E rosettes and almost all E rosette-forming lymphocytes were HTL antigen positive. Conversely HTL antigen-negative cells did not form E rosettes. In contrast, the cells binding EA(IgM)C43 were always HTL antigen negative. There were very few HTL antigen-positive or rosette-forming lymphocytes either with E or EA(IgM)C43 in bone marrow. From these data we conclude that E-rosette-forming and HTL antigen-positive lymphocytes are of thymus origin and EA(IgM)C43-rosette-forming cells are not thymus-dependent cells. ImagesFig. 1 PMID:4579778

  11. Innate Lymphoid Cells in Tumor Immunity

    PubMed Central

    van Beek, Jasper J. P.; Martens, Anne W. J.; Bakdash, Ghaith; de Vries, I. Jolanda M.

    2016-01-01

    Innate lymphoid cells (ILCs) are a group of immune cells of the lymphoid lineage that do not possess antigen specificity. The group includes natural killer (NK) cells, lymphoid tissue inducer (LTi) cells and the recently identified ILC1s, ILC2s and ILC3s. Although the role of NK cells in the context of cancer has been well established, the involvement of other ILC subsets in cancer progression and resistance is just emerging. Here, we review the literature on the role of the different ILC subsets in tumor immunity and discuss its implications for cancer treatment and monitoring. PMID:28536374

  12. Innate Lymphoid Cells in Tumor Immunity.

    PubMed

    van Beek, Jasper J P; Martens, Anne W J; Bakdash, Ghaith; de Vries, I Jolanda M

    2016-02-25

    Innate lymphoid cells (ILCs) are a group of immune cells of the lymphoid lineage that do not possess antigen specificity. The group includes natural killer (NK) cells, lymphoid tissue inducer (LTi) cells and the recently identified ILC1s, ILC2s and ILC3s. Although the role of NK cells in the context of cancer has been well established, the involvement of other ILC subsets in cancer progression and resistance is just emerging. Here, we review the literature on the role of the different ILC subsets in tumor immunity and discuss its implications for cancer treatment and monitoring.

  13. Innate lymphoid cells and their stromal microenvironments.

    PubMed

    Kellermayer, Zoltán; Vojkovics, Dóra; Balogh, Péter

    2017-09-01

    In addition to the interaction between antigen presenting cells, T and B lymphocytes, recent studies have revealed important roles for a diverse set of auxiliary cells that profoundly influence the induction and regulation of immune responses against pathogens. Of these the stromal cells composed of various non-hematopoietic constituents are crucial for the creation and maintenance of specialized semi-static three-dimensional lymphoid tissue microenvironment, whereas the more recently described innate lymphoid cells are generated by the diversification of committed lymphoid precursor cells independently from clonally rearranged antigen receptor genes. Recent findings have revealed important contributions by innate lymphoid cells in inflammation and protection against pathogens in a tissue-specific manner. Importantly, lymphoid stromal cells also influence the onset of immune responses in tissue-specific fashion, raising the possibility of tissue-specific stromal - innate lymphoid cell collaboration. In this review we summarize the main features and interactions between these two cells types, with particular emphasis on ILC type 3 cells and their microenvironmental partners. Copyright © 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  14. Distribution of porcine monocytes in different lymphoid tissues and the lungs during experimental Actinobacillus pleuropneumoniae infection and the role of chemokines

    PubMed Central

    2013-01-01

    Monocytes play an essential role in the defense against bacterial pathogens. Bone marrow (BM) and peripheral blood (PB) monocytes in pigs consist of the main “steady-state” subpopulations: CD14hi/CD163-/SLA-DR- and CD14low/CD163+/SLA-DR+. During inflammation, the subpopulation of “inflammatory” monocytes expressing very high levels of CD163, but lacking the SLA-DR molecule (being CD14low/CD163+/SLA-DR-) appears in the BM and PB and replaces the CD14low/CD163+/SLA-DR+ subpopulation. However, current knowledge of monocyte migration into inflamed tissues in pigs is limited. The aim of the present study was to evaluate the distribution of “inflammatory” CD14low/CD163+/SLA-DR- monocytes during experimental inflammation induced by Actinobacillus pleuropneumoniae (APP) and a possible role for chemokines in attracting “inflammatory” CD14low/CD163+/SLA-DR- monocytes into the tissues. Monocyte subpopulations were detected by flow cytometry. Chemokines and chemokine receptors were detected by RT-qPCR. The “steady-state” monocytes were found in the BM, PB, spleen and lungs of control pigs. After APP-infection, “inflammatory” monocytes replaced the “steady-state” subpopulation in BM, PB, spleen and moreover, they appeared in an unaffected area, demarcation zone and necrotic area of the lungs and in tracheobronchial lymph nodes. They did not appear in mesenteric lymph nodes. Levels of mRNA for various chemokines with their appropriate receptors were found to be elevated in BM (CCL3-CCR1/CCR5, CCL8-CCR2/CCR5, CCL19-CCR7), necrotic area of the lungs (CCL3-CCR1, CCL5-CCR1/CCR3, CCL11-CCR3, CCL22/CCR4) and tracheobronchial lymph nodes (CCL3-CCR1) and therefore they could play a role in attracting monocytes into inflamed tissues. In conclusion, “inflammatory” monocytes appear in different lymphoid tissues and the lungs after APP infection in pigs. Various chemokines could drive this process. PMID:24134635

  15. Migration patterns of dendritic cells in the mouse. Traffic from the blood, and T cell-dependent and -independent entry to lymphoid tissues

    PubMed Central

    1988-01-01

    Dendritic cells (DC) are critical accessory cells for primary immune responses and they may be important stimulators of transplantation reactions, but little is known of their traffic into the tissues. We have studied the migration of purified splenic DC and T lymphocytes, labeled with 111Indium-tropolone, in syngeneic and allogeneic mice. First we demonstrate that DC can migrate from the blood into some lymphoid and nonlymphoid tissues. Immediately after intravenous administration, radio-labeled DC were sequestered in the lungs, but they actively migrated into the liver and spleen and reached equilibrium levels between 3 and 24 h after transfer. At least half of the radiolabel accumulated in the liver, but the spleen was the principal site of DC localization in terms of specific activity (radiolabel per weight of tissue). DC were unable to enter Peyer's patches, or mesenteric and other peripheral lymph nodes from the bloodstream. This was also true in splenectomized recipients, where the otherwise spleen-seeking DC were quantitatively diverted to the liver. In contrast, T cells homed readily to the spleen and lymph nodes of normal mice and increased numbers were present in these tissues in splenectomized mice. Thus, unlike T cells, DC cannot recirculate from blood to lymph via the nodes. We then show that migration of DC from the blood into the spleen is dependent on the presence of T cells: DC did not enter the spleens of nude mice, but when they were reconstituted with T cells the numbers entering the spleen resembled those in euthymic mice. In nude mice, as in splenectomized recipients, the DC that would normally enter the spleen were quantitatively diverted to the liver. These findings suggest that there is a spleen- liver equilibrium for DC, that may be akin to that existing between spleen and lymph node for T cells. Finally, we followed the traffic of radiolabeled DC via the afferent lymphatics after subcutaneous footpad inoculation. DC accumulated in the

  16. Cellular composition of granulomatous lesions in gut-associated lymphoid tissues of goats during the first year after experimental infection with Mycobacterium avium subsp. paratuberculosis.

    PubMed

    Krüger, C; Köhler, H; Liebler-Tenorio, E M

    2015-01-15

    Mycobacterium avium subsp. paratuberculosis (MAP) causes lesions in naturally and experimentally infected ruminants which greatly differ in severity, cellular composition and number of mycobacteria. Morphologically distinct lesions are already found during the clinically inapparent phase of infection. The complex local host response and number of MAP were characterized at the initial sites of lesions, organized gut-associated lymphoid tissue, in experimentally infected goats. Tissues were collected at 3, 6, 9 and 12 month post-inoculation (mpi) from goat kids that had orally received 10 times 10mg of bacterial wet mass of MAP (JII-1961). The cellular composition of lesions in Peyer's patches in the jejunum and next to the ileocecal valve was evaluated in 21 MAP-inoculated goats, where lesions were compared with unaltered tissue of six control goats. CD68+, CD4+, CD8+, γδ T lymphocytes, B lymphocytes and plasma cells, MHC class II+ and CD25+ cells were demonstrated by immunohistochemistry in serial cryostat sections. At 3 mpi, extensive granulomatous infiltrates predominated, consisting of numerous epitheloid cells admixed with many CD4 and γδ T lymphocytes. Only single MAP were detected. This indicates a strong cellular immune reaction able to control MAP infection. γδ T lymphocytes were markedly increased in this type of lesion which may reflect their important role early in the pathogenesis of paratuberculosis. At 9 and 12 mpi, divergent lesions were observed which may reflect different outcomes of host-pathogen interactions. In five goats, minimal granulomatous lesions were surrounded by extensive lymphoplasmacytic infiltrates and no MAP were detected by immunohistochemistry. This was interpreted as effective host response that was able to eliminate MAP locally. In three goats, decreased numbers of lymphocytes, but extensive granulomatous infiltrates with numerous epitheloid cells containing increased numbers of mycobacteria were seen. This shift of the

  17. Long-Term Outcome and Patterns of Failure in Primary Ocular Adnexal Mucosa-Associated Lymphoid Tissue Lymphoma Treated With Radiotherapy

    SciTech Connect

    Hashimoto, Naoki; Sasaki, Ryohei; Nishimura, Hideki; Yoshida, Kenji; Miyawaki, Daisuke; Nakayama, Masao; Uehara, Kazuyuki; Okamoto, Yoshiaki; Ejima, Yasuo; Azumi, Atsushi; Matsui, Toshimitsu; Sugimura, Kazuro

    2012-03-15

    Purpose: To evaluate the long-term treatment outcome and disease behavior of primary ocular adnexal MALT (mucosa-associated lymphoid tissue) lymphoma (POAML) after treatment with radiotherapy. Methods and Materials: Seventy-eight patients (42 male, 36 female) diagnosed with stage I POAML between 1991 and 2010 at Kobe University Hospital were included. The median age was 60 years (range, 22-85 years). The median radiation dose administered was 30.6 Gy. Rituximab-based targeted therapy and/or chemotherapy was performed in 20 patients (25.6%). Local control (LC), recurrence-free survival (RFS), and overall survival (OS) rates were calculated using the Kaplan-Meier method. Results: The median follow-up duration was 66 months. Major tumor sites were conjunctiva in 37 patients (47.4%), orbita in 29 (37.2%), and lacrimal glands in 12 (15.4%). The 5- and 10-year OS rates were 98.1% and 95.3%, respectively. The 5- and 10-year LC rates were both 100%, and the 5- and 10-year RFS rates were 88.5% and 75.9%, respectively. Patients treated with a combination of radiotherapy and targeted therapy and/or chemotherapy had a trend for a better RFS compared with those treated with radiotherapy alone (p = 0.114). None developed greater than Grade 2 acute morbidity. There were 14 patients who experienced Grade 2 morbidities (cataract: 14; retinal disorders: 7; dry eye: 3), 23 patients who had Grade 3 morbidities (cataract: 23; dry eye: 1), and 1 patient who had Grade 4 glaucoma. Conclusions: Radiotherapy for POAML was shown to be highly effective and safe for LC and OS on the basis of long-term observation. The absence of systemic relapse in patients with combined-modality treatment suggests that lower doses of radiation combined with targeted therapy may be worth further study.

  18. Localized Ocular Adnexal Mucosa-Associated Lymphoid Tissue Lymphoma Treated With Radiation Therapy: A Long-Term Outcome in 86 Patients With 104 Treated Eyes

    SciTech Connect

    Harada, Ken; Murakami, Naoya; Kitaguchi, Mayuka; Sekii, Shuhei; Takahashi, Kana; Yoshio, Kotaro; Inaba, Koji; Morota, Madoka; Ito, Yoshinori; Sumi, Minako; Suzuki, Shigenobu; Tobinai, Kensei; Uno, Takashi; Itami, Jun

    2014-03-01

    Purpose: To evaluate the natural history, behavior of progression, prognostic factors, and treatment-related adverse effects of primary ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphoma (POAML). Methods and Materials: Eighty-six patients with histologically proven stage I POAML treated with radiation therapy at National Cancer Center Hospital, Tokyo between 1990 and 2010 were retrospectively reviewed. The median age was 56 years (range, 18-85 years). The median dose administered was 30 Gy (range, 30-46 Gy). Seventy-seven patients (90%) were treated by radiation therapy alone. Results: The median follow-up duration was 9 years (range, 0.9-22 years). The 5- and 10-year overall survival (OS) rates were 97.6% and 93.5%, respectively, and no patients died of lymphoma. Patients with tumor sizes ≥4 cm showed a greater risk of contralateral relapse (P=.012). Six patients with contralateral relapse were seen and treated by radiation therapy alone, and all the lesions were controlled well, with follow-up times of 3 to 12 years. There was 1 case of local relapse after radiation therapy alone, and 3 cases of relapse occurred in a distant site. Cataracts developed in 36 of the 65 eyes treated without lens shielding and in 12 of the 39 patients with lens shielding (P=.037). Conclusions: The majority of patients with POAML showed behavior consistent with that of localized, indolent diseases. Thirty gray of local irradiation seems to be quite effective. The initial bilateral involvement and contralateral orbital relapses can be also controlled with radiation therapy alone. Lens shielding reduces the risk of cataract.

  19. Helicobacter pylori eradication for low-grade gastric mucosa-associated lymphoid tissue lymphoma is more successful in inducing remission in distal compared to proximal disease

    PubMed Central

    Kim, J S; Chung, S J; Choi, Y S; Cheon, J H; Kim, C W; Kim, S G; Jung, H C; Song, I S

    2007-01-01

    A series of studies has shown that Helicobacter pylori eradication induces remission in most patients with low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma. However, there have been few reports about the effect of bacterial treatment on the gastric MALT lymphoma in Korea, a well-known H. pylori endemic area. A total of 111 H. pylori-infected patients were prospectively enrolled in Seoul National University Hospital and 99 among them were completely followed up according to our protocol. After H. pylori eradication, tumoural response was evaluated by endoscopy and histopathology every 2–3 months till complete remission (CR) and every 6 months after achieving CR. Median follow-up period was 41 months (range, 11–125 months). Helicobacter pylori was successfully eradicated in all 99 patients and CR was obtained in 84 (84.8%) of 99 patients. The median time to reach CR was 3 months and 94% of CR is in continuous complete remission. Five patients with CR relapsed after 10–22 months without the evidence of H. pylori reinfection. Cumulative recurrence rate was 2.3, 7.7 and 9.3% at 1, 2 and 3 years, respectively. Tumours were mainly located in distal stomach (67.7%) and tumours in distal stomach were associated with more favourable response than those in proximal stomach (P=0.001). Majority of patients with low-grade gastric MALT lymphoma treated by exclusive H. pylori eradication have a favourable long-term outcome, offering a real chance of cure. Tumour location could be a predictive factor for remission following H. pylori eradication. PMID:17406363

  20. Immunohistochemical comparison of CD5, lambda, and kappa expression in primary and recurrent buccal mucosa-associated lymphoid tissue (MALT) lymphomas.

    PubMed

    Tanaka, Toshiaki; Kitabatake, Kenichirou; Iino, Mituyoshi; Goto, Kaoru

    2011-09-06

    Mucosa-associated lymphoid tissue (MALT) lymphoma is a type of extranodal marginal zone B-cell lymphoma and is a distinct subtype of non-Hodgkin's lymphoma.Primary MALT lymphomas can also occur in the oral cavity, although their appearance in this location is rare. The neoplastic cells of which MALT lymphomas are composed express B-cell antigens and show monotypic immunoglobulin expression with light-chain restriction.Although neoplastic MALT lymphoma cells do not express CD5, previous studies have shown that CD5 positive MALT lymphomas are more prone to dissemination than those that do not express CD5. Moreover, there are some reports that describe kappa- and lambda- dual light chain expression in B cell malignant neoplasms.A 66-year-old Japanese woman with swelling of the right buccal mucosa was referred to our hospital. The lesion was excised and was pathologically diagnosed as a MALT lymphoma tumor with a t(11;18)(q21;q21) chromosome translocation.Swelling of the right buccal mucosa recurred 2 years later. The recurrent tumor was then excised and pathologically diagnosed as MALT lymphoma.Immunohistochemical examination of CD5, lambda, and kappa expressions revealed that the primary tumor was positive for CD5, kappa, and lambda, but the recurrent tumor was weakly positive for CD5 and kappa.With respect to lambda positivity, the recurrent tumor showed negativity.Our study suggests that immunohistochemical expression of CD5, kappa, and lambda in oral MALT lymphoma have the risk of recurrence.We first described the recurrence of CD5 positive MALT lymphoma in the oral cavity and compared the immunohistochemical expressions of CD5, lambda, and kappa between the primary and recurrent tumors.

  1. Mucosa-associated lymphoid tissue gastric lymphoma regression in a renal transplant patient after conversion of the immunosuppression to sirolimus: a case report.

    PubMed

    Lasmar, E P; Coelho, L G V; Lasmar, M F; Lasmar, L F; Lima, P V; Nogueira, A F

    2009-04-01

    The treatment of B-cell non-Hodgkin lymphoma, the most common posttransplant lymphoproliferative disorder, is not well defined. Herein we have reported a case of gastric mucosa-associated lymphoid tissue (MALT) lymphoma with rapid, persistent, and complete remission after conversion of the immunosuppression from cyclosporine (CsA) to sirolimus (SRL). A 42-year-old woman underwent renal transplantation in 1992 with no major abnormalities until 2006 when a gastroscopy performed to investigate dyspeptic symptoms showed a mixed MALT gastric lymphoma (with low- and high-grade components) associated with the presence of Helicobacter pylori infection. Two therapeutic interventions in a 1-week interval were performed: treatment of the H. pylori infection (omeprazole, amoxicillin, and clarithromycin for 14 days) and modification of the immunosuppression by substitution of CsA and azathioprine (AZA) with SRL. Control endoscopy performed 1 month later showed persistence of H. pylori infection and absence of the gastric tumor. New endoscopies performed at 2 and 7 months after therapy confirmed the absence of neoplasia and H. pylori eradication. Currently, the patient has no complaints, displaying a creatinine value of 1.8 mg/dL and a hemoglobin of 9.4 mg/dL using SRL and ibersatan. SRL has been studied extensively as an anticancer drug, acting as a mammalian target for rapamycin (mTOR) inhibitor. Accumulating data support the role of mTOR in lymphomagenesis. In conclusion, our case of gastric MALT lymphoma in a renal transplant patient displayed a complete remission after alteration of the immunosuppressive scheme with the introduction of SRL.

  2. Primary Radiation Therapy in Patients With Localized Orbital Marginal Zone B-Cell Lymphoma of Mucosa-Associated Lymphoid Tissue (MALT Lymphoma)

    SciTech Connect

    Son, Seok Hyun; Choi, Byung Ock; Kim, Gi Won; Yang, Suk Woo; Hong, Young Seon; Choi, Ihl Bohng; Kim, Yeon Sil

    2010-05-01

    Purpose: To evaluate the outcomes of patients with localized orbital marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT lymphoma) who were treated with radiotherapy (RT). Methods and Materials: We retrospectively reviewed the records of 46 patients who were treated with RT for pathologically confirmed localized stage IE marginal zone B-cell lymphoma of MALT. The radiation dose ranged from 21.6 to 45 Gy (median, 30.6 Gy) at 1.8-2.0 Gy per fraction. Median follow-up duration was 32.3 months (range, 3.1-113.6 months). Results: Forty-three patients (93%) achieved complete remission (CR), and three patients (7%) achieved partial remission (PR). Five-year relapse-free survival, cause-specific survival, and overall survival were 93%, 100%, and 100%, respectively. Among the patients with CR, two had recurrence at three sites. One patient relapsed locally and was successfully salvaged with reirradiation. The other patient relapsed in a distant site and was successfully treated with six cycles of CHOP chemotherapy. Late complications were noted in four patients. Two patients developed cataracts at 26 and 37 months after completion of RT. The other two patients developed nasolacrimal duct obstructions at 4 and 11 months after completion of RT. Conclusion: Our study showed that a modest dose of RT is an excellent treatment modality with low complication and recurrence rates. We suggest that a dose of 30.6 Gy is tolerable and sufficient for treating orbital MALT lymphoma. Even following recurrence, successful salvage is possible with RT or chemotherapy.

  3. Radiation Therapy Administration and Survival in Stage I/II Extranodal Marginal Zone B-Cell Lymphoma of Mucosa-Associated Lymphoid Tissue

    SciTech Connect

    Olszewski, Adam J. Desai, Amrita

    2014-03-01

    Purpose: To determine the factors associated with the use of radiation therapy and associated survival outcomes in early-stage marginal zone lymphoma of the mucosa-associated lymphoid tissue (MALT). Methods and Materials: We extracted data on adult patients with stage I/II MALT lymphoma diagnoses between 1998 and 2010 recorded in the Surveillance, Epidemiology, and End Results (SEER) database. We studied factors associated with radiation therapy administration in a logistic regression model and described the cumulative incidence of lymphoma-related death (LRD) according to receipt of the treatment. The association of radiation therapy with survival was explored in multivariate models with adjustment for immortal time bias. Results: Of the 7774 identified patients, 36% received radiation therapy as part of the initial course of treatment. Older patients; black or Hispanic men; white, Hispanic, and black women; and socioeconomically disadvantaged and underinsured patients had a significantly lower chance of receiving radiation therapy. Radiation therapy administration was associated with a lower chance of LRD in most sites. In cutaneous, ocular, and salivary MALT lymphomas, the 5-year estimate of LRD after radiation therapy was 0%. The association of radiation therapy with overall survival in different lymphoma sites was heterogeneous, and statistically significant in cutaneous (hazard ratio 0.45, P=.009) and ocular (hazard ratio 0.47, P<.0001) locations after multivariate adjustment. Conclusions: Demographic factors are associated with the use of radiation therapy in MALT lymphoma. Clinicians should be sensitive to those disparities because the administration of radiation therapy may be associated with improved survival, particularly in cutaneous and ocular lymphomas.

  4. Primary low-grade B-cell lymphoma of mucosa-associated lymphoid tissue of the dura mimicking the presentation of an acute subdural hematoma. Case report and review of the literature.

    PubMed

    Goetz, Pablo; Lafuente, Jesus; Revesz, Tomas; Galloway, Malcolm; Dogan, Ahmet; Kitchen, Neil

    2002-03-01

    The authors present the case of a 64-year-old woman who experienced a left hemiparesis. An initial diagnosis of subdural hematoma was made based on results of computerized tomography scanning. Subsequent magnetic resonance imaging indicated an extraaxial meningioma. Histological findings confirmed an extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT). The authors outline the natural history of central nervous system lymphomas and of MALT lymphomas in other tissues. They review seven previously reported cases and emphasize the importance of recognizing these tumors as a distinct clinicopathological entity.

  5. Endogenous IL-33 is highly expressed in mouse epithelial barrier tissues, lymphoid organs, brain, embryos, and inflamed tissues: in situ analysis using a novel Il-33-LacZ gene trap reporter strain.

    PubMed

    Pichery, Mélanie; Mirey, Emilie; Mercier, Pascale; Lefrancais, Emma; Dujardin, Arnaud; Ortega, Nathalie; Girard, Jean-Philippe

    2012-04-01

    IL-33 (previously known as NF from high endothelial venules) is an IL-1 family cytokine that signals through the ST2 receptor and drives cytokine production in mast cells, basophils, eosinophils, invariant NKT and NK cells, Th2 lymphocytes, and type 2 innate immune cells (natural helper cells, nuocytes, and innate helper 2 cells). Little is known about endogenous IL-33; for instance, the cellular sources of IL-33 in mouse tissues have not yet been defined. In this study, we generated an Il-33-LacZ gene trap reporter strain (Il-33(Gt/Gt)) and used this novel tool to analyze expression of endogenous IL-33 in vivo. We found that the Il-33 promoter exhibits constitutive activity in mouse lymphoid organs, epithelial barrier tissues, brain, and embryos. Immunostaining with anti-IL-33 Abs, using Il-33(Gt/Gt) (Il-33-deficient) mice as control, revealed that endogenous IL-33 protein is highly expressed in mouse epithelial barrier tissues, including stratified squamous epithelia from vagina and skin, as well as cuboidal epithelium from lung, stomach, and salivary gland. Constitutive expression of IL-33 was not detected in blood vessels, revealing the existence of species-specific differences between humans and mice. Importantly, IL-33 protein was always localized in the nucleus of producing cells with no evidence for cytoplasmic localization. Finally, strong expression of the Il-33-LacZ reporter was also observed in inflamed tissues, in the liver during LPS-induced endotoxin shock, and in the lung alveoli during papain-induced allergic airway inflammation. Together, our findings support the possibility that IL-33 may function as a nuclear alarmin to alert the innate immune system after injury or infection in epithelial barrier tissues.

  6. Innate lymphoid cells in atherosclerosis.

    PubMed

    Engelbertsen, Daniel; Lichtman, Andrew H

    2017-04-25

    The family of innate lymphoid cells (ILCs) consisting of NK cells, lymphoid tissue inducer cells and the 'helper'-like ILC subsets ILC1, ILC2 and ILC3 have been shown to have important roles in protection against microbes, regulation of inflammatory diseases and involved in allergic reactions. ILC1s produce IFN-γ upon stimulation with IL-12 and IL-18, ILC2s produce IL-5 and IL-13 responding to IL-33 and IL-25 while ILC3s produce IL-17 and IL-22 after stimulation with IL-23 or IL-1. Although few studies have directly investigated the role for ILCs in atherosclerosis, several studies have investigated transcription factors and cytokines shared by ILCs and T helper cells. In this review we summarize our current understanding of the role of ILC in atherosclerosis and discuss future directions. Copyright © 2017. Published by Elsevier B.V.

  7. Multiple mucosa-associated lymphoid tissue organs involving marginal zone B cell lymphoma: organ-specific relationships and the prognostic factors. Consortium for improving survival of lymphoma study.

    PubMed

    Oh, Sung Yong; Kim, Won Seog; Kim, Jin Seok; Kim, Seok Jin; Lee, Suee; Lee, Dae Ho; Won, Jong-Ho; Hwang, In Gyu; Kim, Min Kyoung; Lee, Soon Il; Chae, Yee Soo; Yang, Deok-Hwan; Kang, Hye Jin; Choi, Chul Won; Park, Jinny; Kim, Hyo Jung; Kwon, Jung Hye; Lee, Ho Sup; Lee, Gyeong-Won; Eom, Hyeon Seok; Kwak, Jae-Yong; Lee, Won Sik; Suh, Cheolwon; Kim, Hyo-Jin

    2010-10-01

    According to a previous review, multiple mucosa-associated lymphoid tissue (MALT)-organs involving marginal zone B cell lymphomas (MZLs) are present in 10-30% of patients. However, the clinical features and specific relationships among involved organs are yet to be clearly identified. In this study, we conducted retrospective analyses of multiple MALT organs involving MZLs (MM-MZLs) to identify their clinical features, treatment, prognosis, and specific relationships among involved organs. For analysis, between June 1987 and June 2009, a total of 55 patients from 17 different institutions in Korea, all of whom were histologically diagnosed with MM-MZL, were included in this study. MM-MZL was defined as MZL involving more than 2 different MALT organs. Multiple involvements within one MALT organ (e.g. both side ocular lesions, multiple lung nodules, and multiple stomach lesions, etc.) were excluded from this study. The male/female ratio of the 55 patients was 41/14. The median age of our subjects was 59 years (range 30-82 years). MM-MZL without lymph node (LN) was detected only in 9 patients (36.2%). Bone marrow (BM) involvement was observed in 17 patients (30.9%). The most common site of involvement was the gastrointestinal (GI) tract (25 patients, 45.5%) followed by the lung (40%), Waldeyer's ring (WR) (27.3%), and ocular area (25.5%). Ocular MZLs were commonly accompanied with WR- or lung-MZLs. GI-MZLs were WR or GI-MZLs. Lung-MZLs were frequently observed with ocular and GI-MZLs. WR-MZLs were ocular or GI-MZLs. A total of 53 patients were treated, and 2 on watchful wait. As much as 48 patients received chemotherapy-based treatment. Among them, CR or PR was achieved in 38 patients (79.2%, 95% CI 67-91%). Median time to progression (TTP) was 2.3 years (95% CI 1.4-3.2 years). Cause-specific overall survival (OS) did not reach the median value. The 5-year OS rate was 84.9%. MM-MZLs tend to be an indolent disease, characterized by prolonged survival with frequent

  8. Effect of in ovo-delivered prebiotics and synbiotics on the morphology and specific immune cell composition in the gut-associated lymphoid tissue.

    PubMed

    Madej, J P; Bednarczyk, M

    2016-01-01

    The purpose of this study was to examine how pre- and synbiotic administration in ovo into the air chamber at d 12 of egg incubation influenced the specific immune cell composition and distribution in the ileum, cecal tonsils (CT) and bursa of Fabricius of broilers. The experiment was performed on 800 hatching eggs of the meat-type chickens (Ross 308). Hatching eggs were treated with: prebiotic, consisting of inulin (Pre1) or Bi(2)tos(®) (Pre2); symbiotic, composed of inulin and Lactococcus lactis subsp. lactis IBB SL1 (Syn1) or Bi(2)tos and Lactococcus lactis subsp. cremoris IBB SC1 (Syn2); or physiological saline as a control group. Seven chickens from each treatment group were randomly selected on , 1, 7, and 21 after hatch for tissue collection. Ileum, cecal tonsil and bursa of Fabricius samples were immunohistochemically stained and the proportions of Bu-1(+), CD3(+), CD4(+), CD8α(+) and TCRγδ(+) cells were estimated. It was indicated that the pre- and synbiotics do not adversely affect the development of the GALT of the chicken. The temporary decrease in B-cell number in bursa on d 7 after hatch suggested an increased colonization rate of the peripheral lymphoid organs by these cells after Pre1, Pre2, and Syn2 treatment. In CT at d 7 after hatch more potent colonization of the GALT by T cells was observed in all pre- and synbiotic treated groups and by B cells in both synbiotic-treated groups than those in respective controls. Then, on d 21 in both synbiotic-treated groups, an increase in T-cell number in ileum was also noticed with faster colonization of the CT by B cells. In 21-day-old chickens, both synbiotics exerted stronger stimulatory effect on the GALT colonization by T cells then prebiotics respectively. Similarly, the colonization by B cells was more pronounced in the Syn2 than in the Pre2 group. The data obtained in this study indicated that prebiotics and particularly synbiotics administrated in ovo stimulated GALT development after hatch.

  9. The biology of innate lymphoid cells.

    PubMed

    Artis, David; Spits, Hergen

    2015-01-15

    The innate immune system is composed of a diverse array of evolutionarily ancient haematopoietic cell types, including dendritic cells, monocytes, macrophages and granulocytes. These cell populations collaborate with each other, with the adaptive immune system and with non-haematopoietic cells to promote immunity, inflammation and tissue repair. Innate lymphoid cells are the most recently identified constituents of the innate immune system and have been the focus of intense investigation over the past five years. We summarize the studies that formally identified innate lymphoid cells and highlight their emerging roles in controlling tissue homeostasis in the context of infection, chronic inflammation, metabolic disease and cancer.

  10. [Splenic lymphoid structures reorganization in gerbils after space flight].

    PubMed

    Grigorenko, D E; Sapin, M R

    2012-01-01

    To assess the effects of weightlessness on the organism of mammals, splenic lymphoid tissue was studied in 10 intact Mongolian gerbils and in 10 animals after a 12-days-long spaceflight. In experimental animals the body mass and splenic, thymic and adrenal mass indexes were sharply reduced. In the spleen, the red pulp area was significantly increased, there appeared the areas of fibrous tissue proliferation, and extensive hemorrhage. Lymphoid nodules with germinal centers disappeared, while periarterial lymphoid sheaths were depleted. Quantitative analysis of cellular content of the lymphoid structures of the spleen showed dramatic activation of cell destruction, lymphocytopoiesis suppression with the disappearance of mitotically dividing cells and a decrease in the number of blast cells. The absence of plasma cells indicates the suppression of the processes of the immunocytopoiesis. The complex of changes noted suggests the decrease of immunological barrier of lymphoid tissue in the spleen and in the whole organism, in gerbils under the conditions of weightlessness in the spaceflight.

  11. Expression of a gp33/27,000 MW activation inducer molecule (AIM) on human lymphoid tissues. Induction of cell proliferation on thymocytes and B lymphocytes by anti-AIM antibodies.

    PubMed Central

    Sánchez-Mateos, P; Cebrián, M; Acevedo, A; López-Botet, M; De Landázuri, M O; Sánchez-Madrid, F

    1989-01-01

    We have recently described several monoclonal antibodies (mAb) that recognize a heterodimeric structure (gp33/27,000 MW) expressed on the surface of human peripheral blood T lymphocytes upon activation with different mitogenic stimuli. Such mAb, when used in combination with submitogenic doses of phorbol ester, were capable of triggering T-cell proliferation. The antigen has been designated as activation inducer molecule (AIM). In the present study we have investigated the expression of the AIM in different lymphoid and non-lymphoid tissues. In addition, we have analysed the ability of lymphocyte subsets derived from thymus and tonsil to proliferate in response to anti-AIM mAb. The presence of AIM on subpopulations of lymphoid cells from thymus, tonsil, lymph node and spleen has been demonstrated by immunoprecipitation, flow cytometry and immunoperoxidase staining of tissue sections. By contrast, non-lymphoid cells from tissue such as brain, kidney, liver, lung or skin did not react with anti-AIM mAb. In thymus, the AIM expression was restricted to a subset of CD3+ medullary thymocytes, whereas CD1+ CD3- cortical thymocytes did not express this antigen. Nevertheless, the majority of both purified CD1- and CD3- thymocytes expressed AIM antigen after treatment with PMA. In tonsil and lymph node, a strong staining of a subset of CD3+ T lymphocytes located in the germinal centre was observed by immunohistochemical labelling with anti-AIM mAb. Certain T cells from the paracortical zone and CD19+ B lymphocytes from mantle region were also reactive. Both purified tonsillar T and B lymphocytes strongly expressed AIM after activation with PMA. The anti-AIM mAb was able to induce a strong proliferative response on purified CD1- thymocytes as well as on both purified tonsillar T and B lymphocytes in the presence of submitogenic doses of PMA. By contrast, no proliferative response was induced through the AIM in the CD3- immature thymocyte subset. Images Figure 1 Figure 3

  12. Total lymphoid irradiation

    SciTech Connect

    Sutherland, D.E.; Ferguson, R.M.; Simmons, R.L.; Kim, T.H.; Slavin, S.; Najarian, J.S.

    1983-05-01

    Total lymphoid irradiation by itself can produce sufficient immunosuppression to prolong the survival of a variety of organ allografts in experimental animals. The degree of prolongation is dose-dependent and is limited by the toxicity that occurs with higher doses. Total lymphoid irradiation is more effective before transplantation than after, but when used after transplantation can be combined with pharmacologic immunosuppression to achieve a positive effect. In some animal models, total lymphoid irradiation induces an environment in which fully allogeneic bone marrow will engraft and induce permanent chimerism in the recipients who are then tolerant to organ allografts from the donor strain. If total lymphoid irradiation is ever to have clinical applicability on a large scale, it would seem that it would have to be under circumstances in which tolerance can be induced. However, in some animal models graft-versus-host disease occurs following bone marrow transplantation, and methods to obviate its occurrence probably will be needed if this approach is to be applied clinically. In recent years, patient and graft survival rates in renal allograft recipients treated with conventional immunosuppression have improved considerably, and thus the impetus to utilize total lymphoid irradiation for its immunosuppressive effect alone is less compelling. The future of total lymphoid irradiation probably lies in devising protocols in which maintenance immunosuppression can be eliminated, or nearly eliminated, altogether. Such protocols are effective in rodents. Whether they can be applied to clinical transplantation remains to be seen.

  13. Immunohistochemical characterization of selected cell markers for the detection of hematopoietic cells in formalin-fixed, paraffin wax-embedded lymphoid tissues of harbor seals (Phoca vitulina) and walruses (Odobenus rosmarus rosmarus).

    PubMed

    Seibel, H; Stimmer, L; Siebert, U; Beineke, A

    2010-10-15

    To facilitate a detailed investigation of pinniped lymphoid organs, 30 monoclonal antibodies (mAb) as well as eight polyclonal antibodies (pAb) of different species specificities directed against cell antigens of the hematopoietic system were tested for immunohistochemical cross-reactivity on formalin-fixed, paraffin wax-embedded tissues of harbor seals (Phoca vitulina) and a walrus (Odobenus rosmarus rosmarus). Six monoclonal and eight polyclonal antibodies showed specific immunoreactivities. Lymphocytes were immunolabeled by an anti-CD3 pAb, anti-Foxp3 mAb and anti-CD79 alpha mAb, while plasma cell subpopulations were recognized by anti-IgA pAb, anti-IgG pAb and anti-IgM pAb as well as by anti-kappa- and anti-lambda light chain pAb. Cells of the histiocytic lineage were recognized by lysozyme-, myeloid/histiocyte antigen-, and CD68-specific markers. Furthermore, dendritic cell-like cells were detected by an anti-S100 protein pAb. The MHC class II antigen was labeled on the majority of immune cells of the harbor seal and walrus using a bovine mAb. Mast cells were stained by an anti-mast cell tryptase mAb. Thus, using these antibodies from various species, it is now possible to determine phenotypical changes in lymphoid organs and detect different leukocyte subsets involved in inflammatory responses in archived tissue samples of these pinniped species.

  14. Ectopic Lymphoid Structures: Powerhouse of Autoimmunity

    PubMed Central

    Corsiero, Elisa; Nerviani, Alessandra; Bombardieri, Michele; Pitzalis, Costantino

    2016-01-01

    Ectopic lymphoid structures (ELS) often develop at sites of inflammation in target tissues of autoimmune diseases, such as rheumatoid arthritis, Sjögren’s syndrome, multiple sclerosis, myasthenia gravis, and systemic lupus erythematosus. ELS are characterized by the formation of organized T/B cells aggregates, which can acquire follicular dendritic cells network supporting an ectopic germinal center response. In this review, we shall summarize the mechanisms that regulate the formation of ELS in tertiary lymphoid organs, with particular emphasis on the role of lymphoid chemokines in both formation and maintenance of ELS, the role of emerging positive and negative regulators of ELS development and function, including T follicular helper cells and IL-27, respectively. Finally, we shall discuss the main functions of ELS in supporting the affinity maturation, clonal selection, and differentiation of autoreactive B cells contributing to the maintenance and perpetuation of humoral autoimmunity. PMID:27799933

  15. [Innate Lymphoid Cells: new actors of immunity].

    PubMed

    Cypowyj, Sophie; Vivier, Éric

    2016-03-01

    The world of lymphocytes has recently expanded. A new group of cells, innate lymphoid cells (ILCs) has been defined. It includes lymphoid cells that have been known for decades, such as natural killer (NK) cells, and lymphoid tissue--inducer (LTi) cells. NK cells recognize a vast array of tumor cells, which they help to eliminate through cytotoxicity and the production of cytokines, such as interferon-γ). (IFN-γ). Advances in our understanding of NK cell biology have led to a growing interest in the clinical manipulation of these cells in cancer. The other ILCs are found mostly in the mucosae and mucosal-associated lymphoid tissues, where they rapidly initiate immune responses to pathogens in the absence of specific sensitization. Here, we outline the basic features of ILCs and review the role of ILCs other than NK cells in cancer. Much of the role of ILCs in cancer remains unknown, but several findings should lead to further efforts to dissect the contribution of different ILC subsets to the promotion, maintenance, or elimination of tumors at various anatomic sites. This will require the development of standardized reagents and protocols for monitoring the presence and function of ILCs in human blood and tissue samples.

  16. Oral administration of drugs with hypersensitivity potential induces germinal center hyperplasia in secondary lymphoid organ/tissue in Brown Norway rats, and this histological lesion is a promising candidate as a predictive biomarker for drug hypersensitivity occurrence in humans

    SciTech Connect

    Tamura, Akitoshi Miyawaki, Izuru; Yamada, Toru; Kimura, Juki; Funabashi, Hitoshi

    2013-08-15

    It is important to evaluate the potential of drug hypersensitivity as well as other adverse effects during the preclinical stage of the drug development process, but validated methods are not available yet. In the present study we examined whether it would be possible to develop a new predictive model of drug hypersensitivity using Brown Norway (BN) rats. As representative drugs with hypersensitivity potential in humans, phenytoin (PHT), carbamazepine (CBZ), amoxicillin (AMX), and sulfamethoxazole (SMX) were orally administered to BN rats for 28 days to investigate their effects on these animals by examinations including observation of clinical signs, hematology, determination of serum IgE levels, histology, and flow cytometric analysis. Skin rashes were not observed in any animals treated with these drugs. Increases in the number of circulating inflammatory cells and serum IgE level did not necessarily occur in the animals treated with these drugs. However, histological examination revealed that germinal center hyperplasia was commonly induced in secondary lymphoid organs/tissues in the animals treated with these drugs. In cytometric analysis, changes in proportions of lymphocyte subsets were noted in the spleen of the animals treated with PHT or CBZ during the early period of administration. The results indicated that the potential of drug hypersensitivity was identified in BN rat by performing histological examination of secondary lymphoid organs/tissues. Data obtained herein suggested that drugs with hypersensitivity potential in humans gained immune reactivity in BN rat, and the germinal center hyperplasia induced by administration of these drugs may serve as a predictive biomarker for drug hypersensitivity occurrence. - Highlights: • We tested Brown Norway rats as a candidate model for predicting drug hypersensitivity. • The allergic drugs did not induce skin rash, whereas D-penicillamine did so in the rats. • Some of allergic drugs increased

  17. Phosphatidylazidothymidine and phosphatidyl-ddC: assessment of uptake in mouse lymphoid tissues and antiviral activities in human immunodeficiency virus-infected cells and in Rauscher leukemia virus-infected mice.

    PubMed Central

    Hostetler, K Y; Richman, D D; Sridhar, C N; Felgner, P L; Felgner, J; Ricci, J; Gardner, M F; Selleseth, D W; Ellis, M N

    1994-01-01

    During the early stages of human immunodeficiency virus (HIV) infection, although symptoms are absent and viral replication in peripheral blood mononuclear cells is low, substantial levels of HIV replication can be documented in lymphoid tissue [G. Pantaleo, C. Graziosi, J.F. Demarest, L. Butini, M. Montroni, C.H. Fox, J.M. Orenstein, D.P. Kotler, and A.S. Fauci, Nature (London) 362:355-358, 1993, and J. Embretsen, M. Zupancic, J.L. Ribas, A. Burke, P. Racz, K. Tenner-Tacz, and A.T. Haase, Nature (London) 362:359-362, 1993]. This observation suggests that earlier treatment of HIV infection may be indicated and that strategies for enhancing drug targeting to the lymphoid tissue reservoris of HIV infection may be beneficial. To address this issue, we synthesized dioleoylphosphatidyl-ddC (DOP-ddC) and dipalmitoylphosphatidyl-3'-azido-3'-deoxythymidine (DPP-AZT), phospholipid prodrugs which form lipid bilayers and which are readily incorporated into liposomes. The anti-HIV activity of DOP-ddC was similar to that of ddC in HIV type 1-infected HT4-6C cells, but DPP-AZT was considerably less active than AZT in HT4-6C cells. Liposomes containing DOP-[3H]ddC or DPP-[3H]AZT administered intraperitoneally to mice produced greater levels of total radioactivity over time in plasma, spleen, and lymphoid tissue relative to the results with [3H]ddC and [3H]AZT, respectively. DPP-AZT administered intraperitoneally in liposomes as a single daily dose to mice infected with Rauscher leukemia virus prevented increased spleen weight and reverse transcriptase levels in serum with a dose-response roughly comparable to that of AZT given continuously in the drinking water. DOP-ddC, DPP-AZT, and lipid conjugates of other antiretroviral nucleosides may provide higher levels of drug over time in plasma and in lymph nodes and spleen, important reservoirs of HIV infection, and may represent an interesting alternative approach to antiviral nucleoside treatment of AIDS. PMID:7695264

  18. Phosphatidylazidothymidine and phosphatidyl-ddC: assessment of uptake in mouse lymphoid tissues and antiviral activities in human immunodeficiency virus-infected cells and in Rauscher leukemia virus-infected mice.

    PubMed

    Hostetler, K Y; Richman, D D; Sridhar, C N; Felgner, P L; Felgner, J; Ricci, J; Gardner, M F; Selleseth, D W; Ellis, M N

    1994-12-01

    During the early stages of human immunodeficiency virus (HIV) infection, although symptoms are absent and viral replication in peripheral blood mononuclear cells is low, substantial levels of HIV replication can be documented in lymphoid tissue [G. Pantaleo, C. Graziosi, J.F. Demarest, L. Butini, M. Montroni, C.H. Fox, J.M. Orenstein, D.P. Kotler, and A.S. Fauci, Nature (London) 362:355-358, 1993, and J. Embretsen, M. Zupancic, J.L. Ribas, A. Burke, P. Racz, K. Tenner-Tacz, and A.T. Haase, Nature (London) 362:359-362, 1993]. This observation suggests that earlier treatment of HIV infection may be indicated and that strategies for enhancing drug targeting to the lymphoid tissue reservoris of HIV infection may be beneficial. To address this issue, we synthesized dioleoylphosphatidyl-ddC (DOP-ddC) and dipalmitoylphosphatidyl-3'-azido-3'-deoxythymidine (DPP-AZT), phospholipid prodrugs which form lipid bilayers and which are readily incorporated into liposomes. The anti-HIV activity of DOP-ddC was similar to that of ddC in HIV type 1-infected HT4-6C cells, but DPP-AZT was considerably less active than AZT in HT4-6C cells. Liposomes containing DOP-[3H]ddC or DPP-[3H]AZT administered intraperitoneally to mice produced greater levels of total radioactivity over time in plasma, spleen, and lymphoid tissue relative to the results with [3H]ddC and [3H]AZT, respectively. DPP-AZT administered intraperitoneally in liposomes as a single daily dose to mice infected with Rauscher leukemia virus prevented increased spleen weight and reverse transcriptase levels in serum with a dose-response roughly comparable to that of AZT given continuously in the drinking water. DOP-ddC, DPP-AZT, and lipid conjugates of other antiretroviral nucleosides may provide higher levels of drug over time in plasma and in lymph nodes and spleen, important reservoirs of HIV infection, and may represent an interesting alternative approach to antiviral nucleoside treatment of AIDS.

  19. Topographic distribution of homing receptors on B and T cells in human gut-associated lymphoid tissue: relation of L-selectin and integrin alpha 4 beta 7 to naive and memory phenotypes.

    PubMed Central

    Farstad, I. N.; Halstensen, T. S.; Kvale, D.; Fausa, O.; Brandtzaeg, P.

    1997-01-01

    In mice, integrin alpha 4 beta 7 is the main receptor used by lymphocytes that home to the Peyer's patches, although L-selectin contributes to the initial interaction with high endothelial venules. Less is known about the expression and function of these adhesion molecules in humans. The distribution of L-selectin and alpha 4 beta 7 on various B- and T-cell subsets was examined in human Peyer's patches (n = 8) and appendix (n = 4), collectively called gut-associated lymphoid tissue. Multicolor immunophenotyping was performed on cryosections, and dispersed cells were examined by flow cytometry. In cryosections, CD45RA+ T cells around and within interfollicular high endothelial venules, as well as surface (s)IgD+ B lymphocytes in the follicle mantles, often expressed abundant L-selectin but only intermediate levels of alpha 4 beta 7. CD45RO+ T cells and sIgD- B cells expressed higher levels of alpha 4 beta 7 and were often located near putative efferent lymphatics; only a small fraction (< 20%) of such memory cells expressed L-selectin. By flow cytometry, considerably more T than B lymphocytes co-expressed L-selectin and alpha 4 beta 7 (40% versus 25% and 67% versus 39%, respectively). In samples with many L-selectin+ cells (> 30%), more of these lymphocytes co-expressed alpha 4 beta 7 than in samples with few L-selectin+ cells. Because L-selectin and alpha 4 beta 7 were co-expressed on lymphocytes located near high endothelial venules, and because such co-expression was relatively common when many L-selectin+ cells were present, both of these molecules might participate in homing to human gut-associated lymphoid tissue. Such homing is probably most pronounced for T lymphocytes that were found to express L-selectin and alpha 4 beta 7 more often than B lymphocytes. The selective and relatively high expression of alpha 4 beta 7 on memory cells located near efferent lymphatics indicated a different migratory capacity; after exit from gut-associated lymphoid tissue, such

  20. Ectopic lymphoid-like structures in infection, cancer and autoimmunity.

    PubMed

    Pitzalis, Costantino; Jones, Gareth W; Bombardieri, Michele; Jones, Simon A

    2014-07-01

    Ectopic lymphoid-like structures often develop at sites of inflammation where they influence the course of infection, autoimmune disease, cancer and transplant rejection. These lymphoid aggregates range from tight clusters of B cells and T cells to highly organized structures that comprise functional germinal centres. Although the mechanisms governing ectopic lymphoid neogenesis in human pathology remain poorly defined, the presence of ectopic lymphoid-like structures within inflamed tissues has been linked to both protective and deleterious outcomes in patients. In this Review, we discuss investigations in both experimental model systems and patient cohorts to provide a perspective on the formation and functions of ectopic lymphoid-like structures in human pathology, with particular reference to the clinical implications and the potential for therapeutic targeting.

  1. Innate lymphoid cells, precursors and plasticity.

    PubMed

    Gronke, Konrad; Kofoed-Nielsen, Michael; Diefenbach, Andreas

    2016-11-01

    Innate lymphoid cells (ILC) have only recently been recognized as a separate entity of the lymphoid lineage. Their subpopulations share common characteristics in terms of early development and major transcriptional circuitry with their related cousins of the T cell world. It is currently hypothesized that ILCs constitute an evolutionary older version of the lymphoid immune system. They are found at all primary entry points for pathogens such as mucosal surfaces of the lung and gastrointestinal system, the skin and the liver, which is the central contact point for pathogens that breach the intestinal barrier and enter the circulation. There, ILC contribute to the first line defense as well as to organ homeostasis. However, ILC are not only involved in classical defense tasks, but also contribute to the organogenesis of lymphoid organs as well as tissue remodeling and even stem cell regeneration. ILC may, therefore, implement different functions according to their emergence in ontogeny, their development and their final tissue location. We will review here their early development from precursors of the fetal liver and the adult bone marrow as well as their late plasticity in adaptation to their environment. Copyright © 2016 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  2. Fat-Associated Lymphoid Clusters in Inflammation and Immunity

    PubMed Central

    Cruz-Migoni, Sara; Caamaño, Jorge

    2016-01-01

    Fat-associated lymphoid clusters (FALCs) are atypical lymphoid tissues that were originally identified in mouse and human mesenteries due to that they contain a high number of type 2 innate lymphoid cells/nuocytes/natural helper cells. FALCs are located on adipose tissues in mucosal surfaces such as the mediastinum, pericardium, and gonadal fat. Importantly, these clusters contain B1, B2 and T lymphocytes as well as myeloid and other innate immune cell populations. The developmental cues of FALC formation have started to emerge, showing that these clusters depend on a different set of molecules and cells than secondary lymphoid tissues for their formation. Here, we review the current knowledge on FALC formation, and we compare FALCs and omental milky spots and their responses to inflammation. PMID:28066422

  3. Innate lymphoid cells in inflammation and immunity.

    PubMed

    McKenzie, Andrew N J; Spits, Hergen; Eberl, Gerard

    2014-09-18

    Innate lymphoid cells (ILCs) were first described as playing important roles in the development of lymphoid tissues and more recently in the initiation of inflammation at barrier surfaces in response to infection or tissue damage. It has now become apparent that ILCs play more complex roles throughout the duration of immune responses, participating in the transition from innate to adaptive immunity and contributing to chronic inflammation. The proximity of ILCs to epithelial surfaces and their constitutive strategic positioning in other tissues throughout the body ensures that, in spite of their rarity, ILCs are able to regulate immune homeostasis effectively. Dysregulation of ILC function might result in chronic pathologies such as allergies, autoimmunity, and inflammation. A new role for ILCs in the maintenance of metabolic homeostasis has started to emerge, underlining their importance in fundamental physiological processes beyond infection and immunity.

  4. Oral administration of drugs with hypersensitivity potential induces germinal center hyperplasia in secondary lymphoid organ/tissue in Brown Norway rats, and this histological lesion is a promising candidate as a predictive biomarker for drug hypersensitivity occurrence in humans.

    PubMed

    Tamura, Akitoshi; Miyawaki, Izuru; Yamada, Toru; Kimura, Juki; Funabashi, Hitoshi

    2013-08-15

    It is important to evaluate the potential of drug hypersensitivity as well as other adverse effects during the preclinical stage of the drug development process, but validated methods are not available yet. In the present study we examined whether it would be possible to develop a new predictive model of drug hypersensitivity using Brown Norway (BN) rats. As representative drugs with hypersensitivity potential in humans, phenytoin (PHT), carbamazepine (CBZ), amoxicillin (AMX), and sulfamethoxazole (SMX) were orally administered to BN rats for 28days to investigate their effects on these animals by examinations including observation of clinical signs, hematology, determination of serum IgE levels, histology, and flow cytometric analysis. Skin rashes were not observed in any animals treated with these drugs. Increases in the number of circulating inflammatory cells and serum IgE level did not necessarily occur in the animals treated with these drugs. However, histological examination revealed that germinal center hyperplasia was commonly induced in secondary lymphoid organs/tissues in the animals treated with these drugs. In cytometric analysis, changes in proportions of lymphocyte subsets were noted in the spleen of the animals treated with PHT or CBZ during the early period of administration. The results indicated that the potential of drug hypersensitivity was identified in BN rat by performing histological examination of secondary lymphoid organs/tissues. Data obtained herein suggested that drugs with hypersensitivity potential in humans gained immune reactivity in BN rat, and the germinal center hyperplasia induced by administration of these drugs may serve as a predictive biomarker for drug hypersensitivity occurrence.

  5. Role of lymphoid chemokines in the development of functional ectopic lymphoid structures in rheumatic autoimmune diseases.

    PubMed

    Corsiero, Elisa; Bombardieri, Michele; Manzo, Antonio; Bugatti, Serena; Uguccioni, Mariagrazia; Pitzalis, Costantino

    2012-07-30

    A sizeable subset of patients with the two most common organ-specific rheumatic autoimmune diseases, rheumatoid arthritis (RA) and Sjögren's syndrome (SS) develop ectopic lymphoid structures (ELS) in the synovial tissue and salivary glands, respectively. These structures are characterized by perivascular (RA) and periductal (SS) clusters of T and B lymphocytes, differentiation of high endothelial venules and networks of stromal follicular dendritic cells (FDC). Accumulated evidence from other and our group demonstrated that the formation and maintenance of ELS in these chronic inflammatory conditions is critically dependent on the ectopic expression of lymphotoxins (LT) and lymphoid chemokines CXCL13, CCL19, CCL21 and CXCL12. In this review we discuss recent advances highlighting the cellular and molecular mechanisms, which regulate the formation of ELS in RA and SS, with particular emphasis on the role of lymphoid chemokines. In particular, we shall focus on the evidence that in the inflammatory microenvironment of the RA synovium and SS salivary glands, several cell types, including resident epithelial, stromal and endothelial cells as well as different subsets of infiltrating immune cells, have been shown to be capable of producing lymphoid chemokines. Finally, we summarize accumulating data supporting the conclusion that ELS in RA and SS represent functional niches for B cells to undergo affinity maturation, clonal selection and differentiation into plasma cells autoreactive against disease-specific antigens, thus contributing to humoral autoimmunity over and above that of secondary lymphoid organs.

  6. Final Results of the IELSG-19 Randomized Trial of Mucosa-Associated Lymphoid Tissue Lymphoma: Improved Event-Free and Progression-Free Survival With Rituximab Plus Chlorambucil Versus Either Chlorambucil or Rituximab Monotherapy.

    PubMed

    Zucca, Emanuele; Conconi, Annarita; Martinelli, Giovanni; Bouabdallah, Reda; Tucci, Alessandra; Vitolo, Umberto; Martelli, Maurizio; Pettengell, Ruth; Salles, Gilles; Sebban, Catherine; Guillermo, Armando Lopez; Pinotti, Graziella; Devizzi, Liliana; Morschhauser, Franck; Tilly, Hervé; Torri, Valter; Hohaus, Stefan; Ferreri, Andrés J M; Zachée, Pierre; Bosly, André; Haioun, Corinne; Stelitano, Caterina; Bellei, Monica; Ponzoni, Maurilio; Copie-Bergman, Christiane; Jack, Andrew; Campo, Elias; Mazzucchelli, Luca; Cavalli, Franco; Johnson, Peter; Thieblemont, Catherine

    2017-03-29

    Purpose There is no consensus on the optimal systemic treatment of patients with extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue. The IELSG-19 phase III study, to our knowledge, was the first such study to address the question of first-line treatment in a randomized trial. Patients and Methods Eligible patients were initially randomly assigned (1:1 ratio) to receive either chlorambucil monotherapy (6 mg/m(2)/d orally on weeks 1 to 6, 9 to 10, 13 to 14, 17 to 18, and 21 to 22) or a combination of chlorambucil (same schedule as above) and rituximab (375 mg/m(2) intravenously on day 1 of weeks 1, 2, 3, 4, 9, 13, 17, and 21). After the planned enrollment of 252 patients, the protocol was amended to continue with a three-arm design (1:1:6 ratio), with a new arm that included rituximab alone (same schedule as the combination arm) and with a final sample size of 454 patients. The main end point was event-free survival (EFS). Analysis of chlorambucil versus the combination arm was performed and reported separately before any analysis of the third arm. Results At a median follow-up of 7.4 years, addition of rituximab to chlorambucil led to significantly better EFS (hazard ratio, 0.54; 95% CI, 0.38 to 0.77). EFS at 5 years was 51% (95% CI, 42 to 60) with chlorambucil alone, 50% (95% CI, 42 to 59) with rituximab alone, and 68% (95% CI, 60 to 76) with the combination ( P = .0009). Progression-free survival was also significantly better with the combination ( P = .0119). Five-year overall survival was approximately 90% in each arm. All treatments were well tolerated. No unexpected toxicities were recorded. Conclusion Rituximab in combination with chlorambucil demonstrated superior efficacy in mucosa-associated lymphoid tissue lymphoma; however, improvements in EFS and progression-free survival did not translate into longer overall survival.

  7. Occupation and lymphoid neoplasms.

    PubMed Central

    La Vecchia, C.; Negri, E.; D'Avanzo, B.; Franceschi, S.

    1989-01-01

    The relationship between occupation and exposure to a number of occupational agents and lymphoid neoplasms was investigated in a case-control study of 69 cases of Hodgkin's disease, 153 non-Hodgkin's lymphomas, 110 multiple myelomas and 396 controls admitted for acute diseases to a network of teaching and general hospitals in the greater Milan area. Among the cases, there was a significant excess of individuals ever occupied in agriculture and food processing: the multivariate relative risks (RR) were 2.1 (95% confidence interval, CI = 1.0-3.8) for Hodgkin's disease, 1.9 (95% CI = 1.2-3.0) for non-Hodgkin's lymphomas and 2.0 (95% CI = 1.1-3.5) for multiple myeloma. Significant trends for duration of exposure to herbicides were observed for lymphomas, but the association was stronger for overall occupation in agriculture than with the specific question of herbicide use. History of occupation in the chemical industry was more frequent among Hodgkin's disease (RR = 4.3, 95% CI = 1.4-10.2), and a significant trend in risk was observed between duration of exposure to benzene and other solvents and multiple myeloma. No significant relation was found between any of the lymphoid neoplasms considered and rubber, dye, painting, printing, tanning leather, photography, pharmaceuticals, wood, coal/gas and nuclear industries. PMID:2789947

  8. Different Pathogenesis of CCR5-Using Primary HIV-1 Isolates from Non-Switch and Switch Virus Patients in Human Lymphoid Tissue Ex Vivo

    NASA Technical Reports Server (NTRS)

    Iarlsson, Ingrid; Grivel, Jean-Charles; Chen. Silvia; Karlsson, Anders; Albert, Jan; Fenyol, Eva Maria; Margolis, Leonid B.

    2005-01-01

    CCR5-utilizing HIV-1 variants (R5) typically transmit infection and dominate its early stages, whereas emergence of CXCR4-using (X4 or R5X4) HIV-1 is often associated with disease progression. However, such a switch in co-receptor usage can only be detected in approximately onehalf of HIV-infected patients (switch virus patients), and progression to immunodeficiency may also occur in patients without detectable switch in co-receptor usage (non-switch virus patients). Here, we used a system of ex vivo-infected tonsillar tissue to compare the pathogenesis of sequential primary R5 HIV-1 isolates from the switch and non-switch patients. Inoculation of ex vivo tissue with these R5 isolates resulted in viral replication and CCR5(+)CD4(+) T cell depletion. The levels of such depletion by HIV-1 isolated from non-switch virus patients were significantly higher than those by R5 HIV-1 isolates from switch virus patients. T cell depletion seemed to be controlled by viral factors and did not significantly vary between tissues from different donors. In contrast, viral replication did not correlate with the switch status of the patients; in tissues fiom different donors it varied 30-fold and seemed to be controlled by a combination of viral and tissue factors. Nevertheless, replication-level hierarchy among sequential isolates remained constant in tissues from various donors. Viral load in vivo was higher in switch virus patients compared to non-switch virus patients. The high cytopathogenicity of CCR5(+)CD4(+) T cells by R5 HIV-1 isolates from non-switch virus patients may explain the steady decline of CD4(+) T cells in the absence of CXCR4 using virus; elimination of target cells by these isolates may limit their own replication in vivo.

  9. Different Pathogenesis of CCR5-Using Primary HIV-1 Isolates from Non-Switch and Switch Virus Patients in Human Lymphoid Tissue Ex Vivo

    NASA Technical Reports Server (NTRS)

    Iarlsson, Ingrid; Grivel, Jean-Charles; Chen. Silvia; Karlsson, Anders; Albert, Jan; Fenyol, Eva Maria; Margolis, Leonid B.

    2005-01-01

    CCR5-utilizing HIV-1 variants (R5) typically transmit infection and dominate its early stages, whereas emergence of CXCR4-using (X4 or R5X4) HIV-1 is often associated with disease progression. However, such a switch in co-receptor usage can only be detected in approximately onehalf of HIV-infected patients (switch virus patients), and progression to immunodeficiency may also occur in patients without detectable switch in co-receptor usage (non-switch virus patients). Here, we used a system of ex vivo-infected tonsillar tissue to compare the pathogenesis of sequential primary R5 HIV-1 isolates from the switch and non-switch patients. Inoculation of ex vivo tissue with these R5 isolates resulted in viral replication and CCR5(+)CD4(+) T cell depletion. The levels of such depletion by HIV-1 isolated from non-switch virus patients were significantly higher than those by R5 HIV-1 isolates from switch virus patients. T cell depletion seemed to be controlled by viral factors and did not significantly vary between tissues from different donors. In contrast, viral replication did not correlate with the switch status of the patients; in tissues fiom different donors it varied 30-fold and seemed to be controlled by a combination of viral and tissue factors. Nevertheless, replication-level hierarchy among sequential isolates remained constant in tissues from various donors. Viral load in vivo was higher in switch virus patients compared to non-switch virus patients. The high cytopathogenicity of CCR5(+)CD4(+) T cells by R5 HIV-1 isolates from non-switch virus patients may explain the steady decline of CD4(+) T cells in the absence of CXCR4 using virus; elimination of target cells by these isolates may limit their own replication in vivo.

  10. Probiotics Differently Affect Gut-Associated Lymphoid Tissue Indolamine-2,3-Dioxygenase mRNA and Cerebrospinal Fluid Neopterin Levels in Antiretroviral-Treated HIV-1 Infected Patients: A Pilot Study

    PubMed Central

    Scagnolari, Carolina; Corano Scheri, Giuseppe; Selvaggi, Carla; Schietroma, Ivan; Najafi Fard, Saeid; Mastrangelo, Andrea; Giustini, Noemi; Serafino, Sara; Pinacchio, Claudia; Pavone, Paolo; Fanello, Gianfranco; Ceccarelli, Giancarlo; Vullo, Vincenzo; d’Ettorre, Gabriella

    2016-01-01

    Recently the tryptophan pathway has been considered an important determinant of HIV-1 infected patients’ quality of life, due to the toxic effects of its metabolites on the central nervous system (CNS). Since the dysbiosis described in HIV-1 patients might be responsible for the microbial translocation, the chronic immune activation, and the altered utilization of tryptophan observed in these individuals, we speculated a correlation between high levels of immune activation markers in the cerebrospinal fluid (CSF) of HIV-1 infected patients and the over-expression of indolamine-2,3-dioxygenase (IDO) at the gut mucosal surface. In order to evaluate this issue, we measured the levels of neopterin in CSF, and the expression of IDO mRNA in gut-associated lymphoid tissue (GALT), in HIV-1-infected patients on effective combined antiretroviral therapy (cART), at baseline and after six months of probiotic dietary management. We found a significant reduction of neopterin and IDO mRNA levels after the supplementation with probiotic. Since the results for the use of adjunctive therapies to reduce the levels of immune activation markers in CSF have been disappointing so far, our pilot study showing the efficacy of this specific probiotic product should be followed by a larger confirmatory trial. PMID:27689995

  11. Post-transplant repopulation of naïve and memory T cells in blood and lymphoid tissue after alemtuzumab-mediated depletion in heart-transplanted cynomolgus monkeys.

    PubMed

    Marco, M R L; Dons, E M; van der Windt, D J; Bhama, J K; Lu, L T; Zahorchak, A F; Lakkis, F G; Cooper, D K C; Ezzelarab, M B; Thomson, A W

    2013-12-01

    Repopulation of memory T cells (Tmem) in allograft recipients after lymphodepletion is a major barrier to transplant tolerance induction. Ineffective depletion of naïve T cells (Tn) and Tmem may predispose to repopulation of Tmem after transplantation. Cynomolgus macaque monkeys given heart allografts were lymphodepleted using Alemtuzumab (Campath-1H; anti-CD52). Peripheral blood (PB) and lymph nodes (LN) were analyzed for CD95(-) (Tn) and CD95(+) cells (Tmem), one day, one month and up to three months after Alemtuzumab infusion. CD52 expression, susceptibility to Alemtuzumab cytotoxicity and pro-apoptotic caspase-3 were evaluated in Tn and Tmem. In vivo, Alemtuzumab induction profoundly depleted lymphocytes in PB (99% reduction) but exerted a lesser effect in LN (70% reduction), with similar depletion of Tn and Tmem subsets. After transplantation, Tmem comprised the majority of lymphocytes in PB and LN. In vitro, LN T cells were more resistant to Alemtuzumab-mediated cytotoxicity than PB lymphocytes. CD4(+) Tn and Tmem were equally susceptible to Alemtuzumab-mediated cytotoxicity, whereas CD8(+) Tn were more resistant than CD8(+) Tmem. However, no significant differences in CD52 expression between lymphocyte subsets in PB and LN were observed. Caspase-3 expression was higher in PB than LN T cells. CD4(+) and CD8(+) Tn expressed lower levels of Caspase-3 than Tmem, in both PB and LN. Thus, after Alemtuzumab infusion, residual Tn in secondary lymphoid tissue may predispose to rapid recovery of Tmem in allograft recipients. © 2013.

  12. Post-transplant repopulation of naïve and memory T cells in blood and lymphoid tissue after alemtuzumab-mediated depletion in heart-transplanted cynomolgus monkeys

    PubMed Central

    Marco, M.R.L.; Dons, E.M.; van der Windt, D.J.; Bhama, J.K.; Lu, L.T.; Zahorchak, A.F.; Lakkis, F.G.; Cooper, D.K.C.; Ezzelarab, M.B.; Thomson, A.W.

    2013-01-01

    Repopulation of memory T cells (Tmem) in allograft recipients after lymphodepletion is a major barrier to transplant tolerance induction. Ineffective depletion of naïve T cells (Tn) and Tmem may predispose to repopulation of Tmem after transplantation. Cynomolgus macaque monkeys given heart allografts were lymphodepleted using Alemtuzumab (Campath-1H; anti-CD52). Peripheral blood (PB) and lymph nodes (LN) were analyzed for CD95− (Tn) and CD95+ cells (Tmem), one day, one month and up to three months after Alemtuzumab infusion. CD52 expression, susceptibility to Alemtuzumab cytotoxicity and pro-apoptotic caspase-3 were evaluated in Tn and Tmem. In vivo, Alemtuzumab induction profoundly depleted lymphocytes in PB (99% reduction) but exerted a lesser effect in LN (70% reduction), with similar depletion of Tn and Tmem subsets. After transplantation, Tmem comprised the majority of lymphocytes in PB and LN. In vitro, LN T cells were more resistant to Alemtuzumabmediated cytotoxicity than PB lymphocytes. CD4+ Tn and Tmem were equally susceptible to Alemtuzumab-mediated cytotoxicity, whereas CD8+ Tn were more resistant than CD8+ Tmem. However, no significant differences in CD52 expression between lymphocyte subsets in PB and LN were observed. Caspase-3 expression was higher in PB than LN T cells. CD4+ and CD8+ Tn expressed lower levels of Caspase-3 than Tmem, in both PB and LN. Thus, after Alemtuzumab infusion, residual Tn in secondary lymphoid tissue may predispose to rapid recovery of Tmem in allograft recipients. PMID:24120957

  13. Anatomical and histological profile of bronchus-associated lymphoid tissue and localization of melatonin receptor types (Mel 1a and Mel 1b) in the lung-associated immune system of a tropical bird, Perdicula asiatica.

    PubMed

    Kumar Kharwar, Rajesh; Haldar, Chandana

    2011-05-01

    The histological distribution of the lung-associated immune system (LAIS) and the expressional pattern of melatonin receptors are still unknown in birds. The aim of the present study was to determine the localization of the bronchus-associated lymphoid tissue (BALT nodule) in a tropical bird, the Indian jungle bush quail, Perdicula asiatica. We also demonstrate the expression of melatonin receptor types (Mel(1a) and Mel(1b)) in order to propose an immunomodulatory role of melatonin in LAIS. Localization of melatonin receptors in the lung of the Indian jungle bush quail, P. asiatica was supported immunohistochemically and by Western blot analysis using specific antibodies for those receptors. Immunolocalization for Mel(1b) receptor was noted in the bronchial region of the lungs, in finger-like projections of mucosal foldings, in lymphocytes in the BALT nodule as well as in free form. In contrast, immunolocalization for Mel(1a) receptor was noted in various areas of the lung instead of in the bronchial region. Western blot analysis showed a single band at 37 and 39kDa for Mel(1a) and Mel(1b) receptors, respectively, with the latter showing higher expression. The results demonstrate a well-developed LAIS and region-specific distribution of melatonin receptors in the lung and provide evidence for a possible functional role for melatonin in the LAIS of birds. Copyright © 2010 Elsevier GmbH. All rights reserved.

  14. Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue with plasma cell differentiation: Periodic acid-schiff reaction-positive Dutcher body is a diagnostic clue to distinguish it from plasmacytoma.

    PubMed

    Nasu, Atsuko; Igawa, Takuro; Sato, Hiaki; Yanai, Hiroyuki; Yoshino, Tadashi; Sato, Yasuharu

    2017-06-01

    We herein report a case of primary parotid extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) with Dutcher bodies. An 82-year-old man presented with a 4 cm × 2.5 cm mass in the left parotid region. Positron emission tomography/computed tomography (PET/CT) showed localized abnormal fluorodeoxyglucose (FDG) uptake in the left parotid gland and lymph nodes of the left cervical region. Fine needle aspiration (FNA) cytology of the left parotid gland showed lymphoplasmacytoid cells with periodic acid-Schiff (PAS)-positive Dutcher bodies. A subsequent excisional biopsy showed sheets of small- to medium-sized neoplastic B cells with abundant IgM in the cytoplasm as detected by immunohistochemistry. A diagnosis of stage II MALT lymphoma was made, but the patient did not receive therapeutic intervention. As previously reported, Dutcher bodies are mainly observed in B-cell neoplasms with IgM production. Because these characteristic intranuclear inclusions can be easily observed by PAS staining, the presence of PAS reaction-positive Dutcher bodies in FNA cytology can serve as a clue to differentially diagnose MALT lymphoma from plasmacytoma. Diagn. Cytopathol. 2017;45:547-551. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  15. Regulation of the adaptive immune system by innate lymphoid cells

    PubMed Central

    Hepworth, Matthew R.; Sonnenberg, Gregory F.

    2014-01-01

    Innate lymphoid cells (ILCs) are a group of lymphocytes that promote rapid cytokine-dependent innate immunity, inflammation and tissue repair. In addition, a growing body of evidence suggests ILCs can influence adaptive immune cell responses. During fetal development a subset of ILCs orchestrate the generation and maturation of secondary lymphoid tissues. Following birth, ILCs continue to modulate adaptive immune cell responses indirectly through interactions with stromal cells in lymphoid tissues and epithelial cells at barrier surfaces. In this review we summarize the current understanding of how ILCs modulate the magnitude and quality of adaptive immune cell responses, and in particular focus on recent evidence suggesting that ILCs can also directly regulate CD4+ T cells. Further, we discuss the implications that these pathways may have on human health and disease. PMID:24594491

  16. Regulation of carbohydrate metabolism in lymphoid tissue. Nature of the endogenous substrates and their contribution to the respiratory fuel of the sliced rat spleen in vitro.

    PubMed

    Suter, D; Weidemann, M J

    1976-04-15

    1. Tissue glycogen contributes, maximally, only 10% of the respiratory fuel of the rat spleen slice in the absence of an added carbon source, and makes no significant contribution when glucose (3mM) is added. 2. The reserves of fatty acid in the form of triglyceride (35.5mumol of fatty acid/g dry wt. of tissue) fall by approx. 25% after incubation of spleen slices with or without added glucose for 2h, and , on this basis, account for 32% of the oxidative fuel. 3. In contrast, the total oxidative contribution of fatty acid reserves to the respiratory fuel, determined on the basis of inhibiton of respiration by 2-bromostearate, is 42-52%. This range includes tissue from both starved and well-fed animals and is not significantly altered by the presence of added glycose (3mM). 4. Large quantities of NH3 (31-35mumol//h per g dry wt. of tissue) are produced by spleen slices incubated in the absence of added substrates, and this value is suppressed by approx. 50% on incubation with glucose (3mM). Adenine nucleotide breakdown can account for only 17% of the total ammonia produced. 5. Individual free amino acid concentrations in spleen were determined, both in vivo and in slices before and after 60 min of incubation. Although the total free amino acid pool size increases by 45% during incubation, owing to protein breakdown, the tissue concentrations of aspartate, glutamate, glutamine and alanine do not increase. It is suggested that these amino acids areoxidized in a net sense to CO2 and water with the liberation of free NH3 via transamination reactions, glutaminase, the purine nucleotide cycle and the tricarboxylic acid cycle. 6. It is concluded that the normal endogenous metabolism of sliced rat spleen (43-52% due to lipids, 30% due to amino acids and 10% due to glycogen) is modified by added glycose only to the extent that glycogen oxidation and 50% of the contribtion made by ino acids are suppressed; endogenous lipid metabolism is unaffected.

  17. Tertiary lymphoid neogenesis is a component of pulmonary lymphoid hyperplasia in patients with common variable immunodeficiency

    PubMed Central

    Maglione, Paul J.; Ko, Huaibin M.; Beasley, Mary B.; Strauchen, James A.; Cunningham-Rundles, Charlotte

    2014-01-01

    Background Despite reducing pneumonia and other infections, antibody replacement does not appear to treat pulmonary lymphoid hyperplasia (PLH) in patients with common variable immunodeficiency (CVID). The pathogenesis and optimal treatments remain to be clarified. Objective We aimed to better understand the pathology of CVID-associated lung disease. Tertiary lymphoneogenesis, although a component of interstitial lung disease associated with autoimmune diseases, has not previously been explored in patients with CVID. Methods We examined the clinical characteristics and pathologic findings of 6 patients with CVID with nodular/infiltrative lung disease who had biopsy specimens demonstrating PLH. Results In these subjects regions of PLH contained distinct Band T-cell zones, with B-cell predominance in 1 patient and T-cell predominance in the others. Colocalization of Ki67, Bcl6, and CD23 within this ectopic lymphoid architecture demonstrated tertiary lymphoneogenesis with active centers of cellular proliferation. One patient received rituximab with improved pulmonary radiologic findings. Conclusion Ectopic lymphoid tissue forming germinal centers suggest tertiary lymphoneogenesis in CVID-associated lung disease. B cell–targeted therapy might disrupt CVID-associated lymphoid hyperplasia. PMID:24131823

  18. Tertiary lymphoid neogenesis is a component of pulmonary lymphoid hyperplasia in patients with common variable immunodeficiency.

    PubMed

    Maglione, Paul J; Ko, Huaibin M; Beasley, Mary B; Strauchen, James A; Cunningham-Rundles, Charlotte

    2014-02-01

    Despite reducing pneumonia and other infections, antibody replacement does not appear to treat pulmonary lymphoid hyperplasia (PLH) in patients with common variable immunodeficiency (CVID). The pathogenesis and optimal treatments remain to be clarified. We aimed to better understand the pathology of CVID-associated lung disease. Tertiary lymphoneogenesis, although a component of interstitial lung disease associated with autoimmune diseases, has not previously been explored in patients with CVID. We examined the clinical characteristics and pathologic findings of 6 patients with CVID with nodular/infiltrative lung disease who had biopsy specimens demonstrating PLH. In these subjects regions of PLH contained distinct B- and T-cell zones, with B-cell predominance in 1 patient and T-cell predominance in the others. Colocalization of Ki67, Bcl6, and CD23 within this ectopic lymphoid architecture demonstrated tertiary lymphoneogenesis with active centers of cellular proliferation. One patient received rituximab with improved pulmonary radiologic findings. Ectopic lymphoid tissue forming germinal centers suggest tertiary lymphoneogenesis in CVID-associated lung disease. B cell-targeted therapy might disrupt CVID-associated lymphoid hyperplasia. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  19. Seeded Amplification of Chronic Wasting Disease Prions in Nasal Brushings and Recto-anal Mucosa-Associated Lymphoid Tissues from Elk by Real-Time Quaking-Induced Conversion.

    PubMed

    Haley, Nicholas J; Siepker, Chris; Hoon-Hanks, Laura L; Mitchell, Gordon; Walter, W David; Manca, Matteo; Monello, Ryan J; Powers, Jenny G; Wild, Margaret A; Hoover, Edward A; Caughey, Byron; Richt, Jürgen A

    2016-04-01

    Chronic wasting disease (CWD), a transmissible spongiform encephalopathy of cervids, was first documented nearly 50 years ago in Colorado and Wyoming and has since been detected across North America and the Republic of Korea. The expansion of this disease makes the development of sensitive diagnostic assays and antemortem sampling techniques crucial for the mitigation of its spread; this is especially true in cases of relocation/reintroduction or prevalence studies of large or protected herds, where depopulation may be contraindicated. This study evaluated the sensitivity of the real-time quaking-induced conversion (RT-QuIC) assay of recto-anal mucosa-associated lymphoid tissue (RAMALT) biopsy specimens and nasal brushings collected antemortem. These findings were compared to results of immunohistochemistry (IHC) analysis of ante- and postmortem samples. RAMALT samples were collected from populations of farmed and free-ranging Rocky Mountain elk (Cervus elaphus nelsoni;n= 323), and nasal brush samples were collected from a subpopulation of these animals (n= 205). We hypothesized that the sensitivity of RT-QuIC would be comparable to that of IHC analysis of RAMALT and would correspond to that of IHC analysis of postmortem tissues. We found RAMALT sensitivity (77.3%) to be highly correlative between RT-QuIC and IHC analysis. Sensitivity was lower when testing nasal brushings (34%), though both RAMALT and nasal brush test sensitivities were dependent on both thePRNPgenotype and disease progression determined by the obex score. These data suggest that RT-QuIC, like IHC analysis, is a relatively sensitive assay for detection of CWD prions in RAMALT biopsy specimens and, with further investigation, has potential for large-scale and rapid automated testing of antemortem samples for CWD.

  20. Stereotypic rheumatoid factors that are frequently expressed in mucosa-associated lymphoid tissue-type lymphomas are rare in the labial salivary glands of patients with Sjögren's syndrome.

    PubMed

    Bende, Richard J; Slot, Linda M; Hoogeboom, Robbert; Wormhoudt, Thera A M; Adeoye, Akanbi O; Guikema, Jeroen E J; van Noesel, Carel J M

    2015-04-01

    Among autoimmune diseases, Sjögren's syndrome (SS) is most strongly associated with the development of malignant B cell lymphoma, in particular mucosa-associated lymphoid tissue (MALT)-type lymphoma. Previously, we have shown that in ∼40% of cases of salivary gland MALT lymphoma, high-affinity stereotypic rheumatoid factor (RF) B cell receptors, specific for IgG-Fc, are expressed. This study was undertaken to investigate whether in the inflamed salivary glands of patients with SS, a similar RF-biased Ig repertoire is present. Extensive analyses of the B cell Ig VH region repertoire were performed on microdissected tissue samples from the labial salivary glands of 4 patients with SS. All SS labial salivary glands harbored expanded B cell clones, of which 1 or 2 were highly expanded and detected in >50% of the microdissected samples. However, among the identified 464 distinct Ig clonotypes, only 3 stereotypic RF-expressing clones were detected. In 2 patients with SS, an RF-expressing clone was detected at low frequency in 1 of the microdissected samples, whereas 1 patient with SS harbored a highly expanded RF-expressing clone that was detected in all microdissected samples and also detected in the peripheral blood. Two years after analysis of this sample, the latter patient developed a diffuse large B cell lymphoma originating from the same RF clone. Inflamed labial salivary glands in patients with SS generally harbor 1 or 2 highly expanded B cell clones. The repertoire strongly biased toward stereotypic RFs in salivary gland MALT lymphomas is not a reflection of a similar repertoire in the inflamed salivary glands of patients with SS; rather, in the latter, the repertoire is based on a strong selection advantage of incidental stereotypic RF-expressing B cells. Copyright © 2015 by the American College of Rheumatology.

  1. Seeded Amplification of Chronic Wasting Disease Prions in Nasal Brushings and Recto-anal Mucosa-Associated Lymphoid Tissues from Elk by Real-Time Quaking-Induced Conversion

    PubMed Central

    Siepker, Chris; Hoon-Hanks, Laura L.; Mitchell, Gordon; Walter, W. David; Manca, Matteo; Monello, Ryan J.; Powers, Jenny G.; Wild, Margaret A.; Hoover, Edward A.; Caughey, Byron; Richt, Jürgen A.

    2016-01-01

    Chronic wasting disease (CWD), a transmissible spongiform encephalopathy of cervids, was first documented nearly 50 years ago in Colorado and Wyoming and has since been detected across North America and the Republic of Korea. The expansion of this disease makes the development of sensitive diagnostic assays and antemortem sampling techniques crucial for the mitigation of its spread; this is especially true in cases of relocation/reintroduction or prevalence studies of large or protected herds, where depopulation may be contraindicated. This study evaluated the sensitivity of the real-time quaking-induced conversion (RT-QuIC) assay of recto-anal mucosa-associated lymphoid tissue (RAMALT) biopsy specimens and nasal brushings collected antemortem. These findings were compared to results of immunohistochemistry (IHC) analysis of ante- and postmortem samples. RAMALT samples were collected from populations of farmed and free-ranging Rocky Mountain elk (Cervus elaphus nelsoni; n = 323), and nasal brush samples were collected from a subpopulation of these animals (n = 205). We hypothesized that the sensitivity of RT-QuIC would be comparable to that of IHC analysis of RAMALT and would correspond to that of IHC analysis of postmortem tissues. We found RAMALT sensitivity (77.3%) to be highly correlative between RT-QuIC and IHC analysis. Sensitivity was lower when testing nasal brushings (34%), though both RAMALT and nasal brush test sensitivities were dependent on both the PRNP genotype and disease progression determined by the obex score. These data suggest that RT-QuIC, like IHC analysis, is a relatively sensitive assay for detection of CWD prions in RAMALT biopsy specimens and, with further investigation, has potential for large-scale and rapid automated testing of antemortem samples for CWD. PMID:26888899

  2. Evaluation of a panel of antibodies for the immunohistochemical identification of immune cells in paraffin-embedded lymphoid tissues of new- and old-world camelids.

    PubMed

    Uhde, Ann-Kathrin; Lehmbecker, Annika; Baumgärtner, Wolfgang; Spitzbarth, Ingo

    2017-02-01

    Different species of camelids play an important role in the epidemiology of various emerging infectious diseases such as Middle East respiratory syndrome. For precise investigations of the immunopathogenesis in these host species, appropriate immunohistochemical markers are highly needed in order to phenotype distinct immune cells populations in camelids. So far, specific immunohistochemical markers for camelid immune cells are rarely commercially available, and cross-reactivity studies are restricted to the use of frozen dromedary tissues. To bridge this gap, 14 commercially available primary antibodies were tested for their suitability to demonstrate immune cell populations on formalin fixed paraffin-embedded (FFPE) tissue sections of dromedaries, Bactrian camels, llamas, and alpacas in the present study. Out of these, 9 antibodies directed against CD3, CD20, CD79α, HLA-DR, Iba-1, myeloid/histiocyte antigen, CD204, CD208, and CD68 antigen exhibited distinct immunoreaction patterns to certain camelid immune cell subsets. The distribution of these antigens was comparatively evaluated in different anatomical compartments of thymus, spleen, mesenteric, and tracheobronchial lymph nodes. The presented results will provide a basis for further investigations in camelids, especially with respect to the role of the immune response in certain infectious diseases, which harbor a considerable risk to spill over to other species. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. 'Trained immunity': consequences for lymphoid malignancies.

    PubMed

    Stevens, Wendy B C; Netea, Mihai G; Kater, Arnon P; van der Velden, Walter J F M

    2016-12-01

    In hematological malignancies complex interactions exist between the immune system, microorganisms and malignant cells. On one hand, microorganisms can induce cancer, as illustrated by specific infection-induced lymphoproliferative diseases such as Helicobacter pylori-associated gastric mucosa-associated lymphoid tissue lymphoma. On the other hand, malignant cells create an immunosuppressive environment for their own benefit, but this also results in an increased risk of infections. Disrupted innate immunity contributes to the neoplastic transformation of blood cells by several mechanisms, including the uncontrolled clearance of microbial and autoantigens resulting in chronic immune stimulation and proliferation, chronic inflammation, and defective immune surveillance and anti-cancer immunity. Restoring dysfunction or enhancing responsiveness of the innate immune system might therefore represent a new angle for the prevention and treatment of hematological malignancies, in particular lymphoid malignancies and associated infections. Recently, it has been shown that cells of the innate immune system, such as monocytes/macrophages and natural killer cells, harbor features of immunological memory and display enhanced functionality long-term after stimulation with certain microorganisms and vaccines. These functional changes rely on epigenetic reprogramming and have been termed 'trained immunity'. In this review the concept of 'trained immunity' is discussed in the setting of lymphoid malignancies. Amelioration of infectious complications and hematological disease progression can be envisioned to result from the induction of trained immunity, but future studies are required to prove this exciting new hypothesis. Copyright© Ferrata Storti Foundation.

  4. Tertiary Lymphoid Structures in Cancers: Prognostic Value, Regulation, and Manipulation for Therapeutic Intervention

    PubMed Central

    Sautès-Fridman, Catherine; Lawand, Myriam; Giraldo, Nicolas A.; Kaplon, Hélène; Germain, Claire; Fridman, Wolf Herman; Dieu-Nosjean, Marie-Caroline

    2016-01-01

    Tertiary lymphoid structures (TLS) are ectopic lymphoid aggregates that reflect lymphoid neogenesis occurring in tissues at sites of inflammation. They are detected in tumors where they orchestrate local and systemic anti-tumor responses. A correlation has been found between high densities of TLS and prolonged patient’s survival in more than 10 different types of cancer. TLS can be regulated by the same set of chemokines and cytokines that orchestrate lymphoid organogenesis and by regulatory T cells. Thus, TLS offer a series of putative new targets that could be used to develop therapies aiming to increase the anti-tumor immune response. PMID:27752258

  5. Effect of a cocoa diet on the small intestine and gut-associated lymphoid tissue composition in an oral sensitization model in rats.

    PubMed

    Camps-Bossacoma, Mariona; Pérez-Cano, Francisco J; Franch, Àngels; Untersmayr, Eva; Castell, Margarida

    2017-04-01

    Previous studies have attributed to the cocoa powder the capacity to attenuate the immune response in a rat oral sensitization model. To gain a better understanding of cocoa-induced mechanisms at small intestinal level, 3-week-old female Lewis rats were fed either a standard diet or a diet containing 10% cocoa for 4 weeks with or without concomitant oral sensitization with ovalbumin (OVA). Thereafter, we evaluated the lymphocyte composition of the Peyer's patches (PPL), small intestine epithelium (IEL) and lamina propria (LPL). Likewise, gene expression of several immune molecules was quantified in the small intestine. Moreover, histological samples were used to evaluate the proportion of goblet cells, IgA+ cells and granzyme+cells as well. In cocoa-fed animals, we identified a five-time reduction in the percentage of IgA+ cells in intestinal tissue together with a decreased proportion of TLR4+ IEL. Analyzing the lymphocyte composition, almost a double proportion of TCRγδ+cells and an increase of NK cell percentage in PPL and IEL were found. In addition, a rise in CD25+, CD103+ and CD62L- cell proportions was observed in CD4+ PPL from cocoa-fed animals, along with a decrease in gene expression of CD11b, CD11c and IL-10. These results suggest that changes in PPL and IEL composition and in the gene expression induced by the cocoa diet could be involved, among other mechanisms, on its tolerogenic effect.

  6. Dietary supplementation with Bifidobacterium lactis NCC2818 from weaning reduces local immunoglobulin production in lymphoid-associated tissues but increases systemic antibodies in healthy neonates.

    PubMed

    Lewis, Marie C; Patel, Dilip V; Fowler, Jenni; Duncker, Swantje; Zuercher, Adrian W; Mercenier, Annick; Bailey, Mick

    2013-10-01

    Weaning is associated with a major shift in the microbial community of the intestine, and this instability may make it more acquiescent than the adult microbiota to long-term changes. Modulation achieved through dietary interventions may have potentially beneficial effects on the developing immune system, which is driven primarily by the microbiota. The specific aim of the present study was to determine whether immune development could be modified by dietary supplementation with the human probiotic Bifidobacterium lactis NCC2818 in a tractable model of weaning in infants. Piglets were reared by their mothers before being weaned onto a solid diet supplemented with B. lactis NCC2818, while sibling controls did not receive supplementation. Probiotic supplementation resulted in a reduction in IgA (P<0·0005) and IgM (P<0·009) production by mucosal tissues but had no effect on IgG production (P>0·05). Probiotic-supplemented pigs had more mast cells than unsupplemented littermates (P<0·0001), although numbers in both groups were low. In addition, the supplemented piglets made stronger serum IgG responses to fed and injected antigens (P<0·05). The present findings are consistent with B. lactis NCC2818 reducing intestinal permeability induced by weaning, and suggest that the piglet is a valuable intermediate between rodent models and human infants. The results also strongly suggest that measures of the effect of probiotic supplementation on the immune system need to be interpreted carefully as proxy measures of health benefit. However, they are useful in developing an understanding of the mechanism of action of probiotic strains, an important factor in predicting favourable health outcomes of nutritional intervention.

  7. Norisoboldine ameliorates collagen-induced arthritis through regulating the balance between Th17 and regulatory T cells in gut-associated lymphoid tissues.

    PubMed

    Tong, Bei; Dou, Yannong; Wang, Ting; Yu, Juntao; Wu, Xin; Lu, Qian; Chou, Guixin; Wang, Zhengtao; Kong, Lingyi; Dai, Yue; Xia, Yufeng

    2015-01-01

    Norisoboldine (NOR), the main active ingredient of the dry root of Lindera aggregata, was previously proven to have substantial therapeutic effects on collagen-induced arthritis (CIA) in mice by oral administration. However, it exhibited a very poor bioavailability in normal rats. The pharmacokinetic-pharmacodynamics disconnection attracts us to explore its anti-arthritic mechanism in more detail. In this study, NOR, administered orally, markedly attenuated the pathological changes in CIA rats, which was accompanied by the down-regulation of pro-inflammatory cytokines and the up-regulation of anti-inflammatory cytokine IL-10. Pharmacokinetic studies demonstrated that the plasma concentration of NOR was moderately elevated in CIA rats compared with normal rats, but it was still far lower than the minimal effective concentration required for inhibiting the proliferation and activation of T lymphocytes in vitro. Interestingly, NOR was shown to regulate the balance between Th17 and regulatory T (Treg) cells in the intestinal lymph nodes more strikingly than in other tissues. It could increase the expression of Foxp3 mRNA in both gut and joints, and markedly up-regulate the number of integrin α4β7 (a marker of gut source)-positive Foxp3(+) cells in the joints of CIA rats. These results suggest that the gut might be the primary action site of NOR, and NOR exerts anti-arthritis effect through regulating the balance between Th17 and Treg cells in intestinal lymph nodes and yielding a trafficking of lymphocytes (especially Treg cells) from the gut to joint. The findings of the present study also provide a plausible explanation for the anti-arthritic effects of poorly absorbed compounds like NOR.

  8. Norisoboldine ameliorates collagen-induced arthritis through regulating the balance between Th17 and regulatory T cells in gut-associated lymphoid tissues

    SciTech Connect

    Tong, Bei; Dou, Yannong; Wang, Ting; Yu, Juntao; Wu, Xin; Lu, Qian; Chou, Guixin; Wang, Zhengtao; Kong, Lingyi; Dai, Yue; Xia, Yufeng

    2015-01-01

    Norisoboldine (NOR), the main active ingredient of the dry root of Lindera aggregata, was previously proven to have substantial therapeutic effects on collagen-induced arthritis (CIA) in mice by oral administration. However, it exhibited a very poor bioavailability in normal rats. The pharmacokinetic–pharmacodynamics disconnection attracts us to explore its anti-arthritic mechanism in more detail. In this study, NOR, administered orally, markedly attenuated the pathological changes in CIA rats, which was accompanied by the down-regulation of pro-inflammatory cytokines and the up-regulation of anti-inflammatory cytokine IL-10. Pharmacokinetic studies demonstrated that the plasma concentration of NOR was moderately elevated in CIA rats compared with normal rats, but it was still far lower than the minimal effective concentration required for inhibiting the proliferation and activation of T lymphocytes in vitro. Interestingly, NOR was shown to regulate the balance between Th17 and regulatory T (Treg) cells in the intestinal lymph nodes more strikingly than in other tissues. It could increase the expression of Foxp3 mRNA in both gut and joints, and markedly up-regulate the number of integrin α4β7 (a marker of gut source)-positive Foxp3{sup +} cells in the joints of CIA rats. These results suggest that the gut might be the primary action site of NOR, and NOR exerts anti-arthritis effect through regulating the balance between Th17 and Treg cells in intestinal lymph nodes and yielding a trafficking of lymphocytes (especially Treg cells) from the gut to joint. The findings of the present study also provide a plausible explanation for the anti-arthritic effects of poorly absorbed compounds like NOR. - Highlights: • Norisoboldine, administered orally, markedly attenuates the clinical signs of CIA. • Norisoboldine regulates the balance of Th17/Treg cells in the intestinal lymph node. • Norisoboldine induces the migration of Treg cells from the gut to joint.

  9. High Endothelial Venules and Other Blood Vessels: Critical Regulators of Lymphoid Organ Development and Function

    PubMed Central

    Ager, Ann

    2017-01-01

    The blood vasculature regulates both the development and function of secondary lymphoid organs by providing a portal for entry of hemopoietic cells. During the development of lymphoid organs in the embryo, blood vessels deliver lymphoid tissue inducer cells that initiate and sustain the development of lymphoid tissues. In adults, the blood vessels are structurally distinct from those in other organs due to the requirement for high levels of lymphocyte recruitment under non-inflammatory conditions. In lymph nodes (LNs) and Peyer’s patches, high endothelial venules (HEVs) especially adapted for lymphocyte trafficking form a spatially organized network of blood vessels, which controls both the type of lymphocyte and the site of entry into lymphoid tissues. Uniquely, HEVs express vascular addressins that regulate lymphocyte entry into lymphoid organs and are, therefore, critical to the function of lymphoid organs. Recent studies have demonstrated important roles for CD11c+ dendritic cells in the induction, as well as the maintenance, of vascular addressin expression and, therefore, the function of HEVs. Tertiary lymphoid organs (TLOs) are HEV containing LN-like structures that develop inside organized tissues undergoing chronic immune-mediated inflammation. In autoimmune lesions, the development of TLOs is thought to exacerbate disease. In cancerous tissues, the development of HEVs and TLOs is associated with improved patient outcomes in several cancers. Therefore, it is important to understand what drives the development of HEVs and TLOs and how these structures contribute to pathology. In several human diseases and experimental animal models of chronic inflammation, there are some similarities between the development and function of HEVs within LN and TLOs. This review will summarize current knowledge of how hemopoietic cells with lymphoid tissue-inducing, HEV-inducing, and HEV-maintaining properties are recruited from the bloodstream to induce the development and

  10. Stromal cells in chronic inflammation and tertiary lymphoid organ formation.

    PubMed

    Buckley, Christopher D; Barone, Francesca; Nayar, Saba; Bénézech, Cecile; Caamaño, Jorge

    2015-01-01

    Inflammation is an unstable state. It either resolves or persists. Why inflammation persists and the factors that define tissue tropism remain obscure. Increasing evidence suggests that tissue-resident stromal cells not only provide positional memory but also actively regulate the differential accumulation of inflammatory cells within inflamed tissues. Furthermore, at many sites of chronic inflammation, structures that mimic secondary lymphoid tissues are observed, suggesting that chronic inflammation and lymphoid tissue formation share common activation programs. Similarly, blood and lymphatic endothelial cells contribute to tissue homeostasis and disease persistence in chronic inflammation. This review highlights our increasing understanding of the role of stromal cells in inflammation and summarizes the novel immunological role that stromal cells exert in the persistence of inflammatory diseases.

  11. Genetic errors of the human caspase recruitment domain-B-cell lymphoma 10-mucosa-associated lymphoid tissue lymphoma-translocation gene 1 (CBM) complex: Molecular, immunologic, and clinical heterogeneity.

    PubMed

    Pérez de Diego, Rebeca; Sánchez-Ramón, Silvia; López-Collazo, Eduardo; Martínez-Barricarte, Rubén; Cubillos-Zapata, Carolina; Ferreira Cerdán, Antonio; Casanova, Jean-Laurent; Puel, Anne

    2015-11-01

    Three members of the caspase recruitment domain (CARD) family of adaptors (CARD9, CARD10, and CARD11) are known to form heterotrimers with B-cell lymphoma 10 (BCL10) and mucosa-associated lymphoid tissue lymphoma-translocation gene 1 (MALT1). These 3 CARD-BCL10-MALT1 (CBM) complexes activate nuclear factor κB in both the innate and adaptive arms of immunity. Human inherited defects of the 3 components of the CBM complex, including the 2 adaptors CARD9 and CARD11 and the 2 core components BCL10 and MALT1, have recently been reported. Biallelic loss-of-function mutant alleles underlie several different immunologic and clinical phenotypes, which can be assigned to 2 distinct categories. Isolated invasive fungal infections of unclear cellular basis are associated with CARD9 deficiency, whereas a broad range of clinical manifestations, including those characteristic of T- and B-lymphocyte defects, are associated with CARD11, MALT1, and BCL10 deficiencies. Interestingly, human subjects with these mutations have some features in common with the corresponding knockout mice, but other features are different between human subjects and mice. Moreover, germline and somatic gain-of-function mutations of MALT1, BCL10, and CARD11 have also been found in patients with other lymphoproliferative disorders. This broad range of germline and somatic CBM lesions, including loss-of-function and gain-of-function mutations, highlights the contribution of each of the components of the CBM complex to human immunity. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  12. Synergistic effect of programmed cell death protein 1 blockade and secondary lymphoid tissue chemokine in the induction of anti-tumor immunity by a therapeutic cancer vaccine.

    PubMed

    Moeini, Soheila; Saeidi, Mohsen; Fotouhi, Fatemeh; Mondanizadeh, Mahdieh; Shirian, Sadegh; Mohebi, Alireza; Gorji, Ali; Ghaemi, Amir

    2017-02-01

    The use of DNA vaccines has become an attractive approach for generating antigen-specific cytotoxic CD8(+) T lymphocytes (CTLs), which can mediate protective antitumor immunity. The potency of DNA vaccines encoding weakly immunogenic tumor-associated antigens (TAAs) can be improved by using an adjuvant injected together with checkpoint antibodies. In the current study, we evaluated whether the therapeutic effects of a DNA vaccine encoding human papilloma virus type 16 (HPV-16) E7 can be enhanced by combined application of an immune checkpoint blockade directed against the programmed death-1 (PD-1) pathway and secondary lymphoid tissue chemokine (SLC) also known as CCL21 adjuvant, in a mouse cervical cancer model. The therapeutic effects of the DNA vaccine in combination with CCL21 adjuvant plus PD-1 blockade was evaluated using a tumor growth curve. To further investigate the mechanism underlying the antitumor response, cytolytic and lymphocyte proliferation responses in splenocytes were measured using non-radioactive cytotoxicity and MTT assays, respectively. Vascular endothelial growth factor (VEGF) and IL-10 expression in the tumor and the levels of IFN-γ and IL-4 in supernatants of spleno-lymphocyte cultures were measured using ELISA. The immune efficacy was evaluated by in vivo tumor regression assay. The results showed that vaccination with a DNA vaccine in combination with the CCL21 adjuvant plus PD-1 blockade greatly enhanced cytotoxic T lymphocyte production and lymphocyte proliferation rates and greatly inhibited tumor progression. Moreover, the vaccine in combination with adjuvant and blockade significantly reduced intratumoral VEGF, IL-10 and splenic IL-4 but induced the expression of splenic IFN-γ. This formulation could be an effective candidate for a vaccine against cervical cancers and merits further investigation.

  13. Prion pathogenesis and secondary lymphoid organs (SLO)

    PubMed Central

    Mabbott, Neil A.

    2012-01-01

    Prion diseases are subacute neurodegenerative diseases that affect humans and a range of domestic and free-ranging animal species. These diseases are characterized by the accumulation of PrPSc, an abnormally folded isoform of the cellular prion protein (PrPC), in affected tissues. The pathology during prion disease appears to occur almost exclusively within the central nervous system. The extensive neurodegeneration which occurs ultimately leads to the death of the host. An intriguing feature of the prion diseases, when compared with other protein-misfolding diseases, is their transmissibility. Following peripheral exposure, some prion diseases accumulate to high levels within lymphoid tissues. The replication of prions within lymphoid tissue has been shown to be important for the efficient spread of disease to the brain. This article describes recent progress in our understanding of the cellular mechanisms that influence the propagation of prions from peripheral sites of exposure (such as the lumen of the intestine) to the brain. A thorough understanding of these events will lead to the identification of important targets for therapeutic intervention, or alternatively, reveal additional processes that influence disease susceptibility to peripherally-acquired prion diseases. PMID:22895090

  14. Detection of Quiescent Infections with Multiple Elephant Endotheliotropic Herpesviruses (EEHVs), Including EEHV2, EEHV3, EEHV6, and EEHV7, within Lymphoid Lung Nodules or Lung and Spleen Tissue Samples from Five Asymptomatic Adult African Elephants

    PubMed Central

    Zong, Jian-Chao; Heaggans, Sarah Y.; Long, Simon Y.; Latimer, Erin M.; Nofs, Sally A.; Bronson, Ellen; Casares, Miguel; Fouraker, Michael D.; Pearson, Virginia R.; Richman, Laura K.

    2015-01-01

    involves a variety of strains of EEHV1, whose natural host has been unclear. Here, we carried out genotype analyses by partial PCR sequencing of necropsy tissue from five asymptomatic African elephants and identified multiple simultaneous infections by several different EEHV types, including high concentrations in lymphoid lung nodules. Overall, the results provide strong evidence that EEHV2, EEHV3, EEHV6, and EEHV7 represent natural ubiquitous infections in African elephants, whereas Asian elephants harbor EEHV1A, EEHV1B, EEHV4, and EEHV5. Although a single case of fatal cross-species infection by EEHV3 is known, the results do not support the previous concept that highly pathogenic EEHV1A crossed from African to Asian elephants in zoos. PMID:26719245

  15. Lymphoid Neogenesis and Tertiary Lymphoid Organs in Transplanted Organs

    PubMed Central

    Koenig, Alice; Thaunat, Olivier

    2016-01-01

    The progressive organization of immune effectors into functional ectopic lymphoid structures, named tertiary lymphoid organs (TLO), has been observed in many conditions in which target antigens fail to be eliminated by the immune system. Not surprisingly, TLO have been recurrently identified in chronically rejected allografts. Although significant progress has been made over the last decades in understanding the molecular mechanisms involved in TLO development (a process named lymphoid neogenesis), the role of intragraft TLO (if any) in chronic rejection remains elusive. The prevailing dogma is that TLO contribute to graft rejection by generating and propagating local humoral and cellular alloimmune responses. However, TLO have been recently observed in long-term accepting allografts, suggesting that they might also be able to regulate alloimmune responses. In this review, we discuss our current understanding of how TLO are induced and propose a unified model in which TLO can play deleterious or regulatory roles and therefore actively modulate the kinetics of chronic rejection. PMID:28082981

  16. Mechanisms of organogenesis of primary lymphoid follicles.

    PubMed

    Beyer, Tilo; Meyer-Hermann, Michael

    2008-04-01

    Primary lymphoid follicles (PLFs) in secondary lymphoid tissue (SLT) of mammals are the backbone for the formation of follicular dendritic cell (FDC) networks. These are important for germinal center reactions during which affinity maturation creates optimized antibodies in adaptive immune responses. In the context of organogenesis, molecular requirements for the formation of follicles have been identified. The present study complements these findings with a simulation of the dynamics of the PLF formation, and a critical analysis of the relevant molecular interactions. In contrast to other problems of pattern formation, the homeostasis of cell populations in SLTs is not governed by a growth-death balance but by a flow equilibrium of migrating cells. The influx of cells into these tissues has been extensively studied. However, less information is available about the efflux of lymphocytes from SLTs. This study formulates the minimal requirements for cell efflux that guarantee a flow equilibrium and, thus, a stable PLF. The model predicts that in addition to already identified regulatory mechanisms, a negative regulation of the generation of FDCs is required. Furthermore, a comparison with data concerning the microanatomy of SLTs yields the conclusion that dynamical changes of the lymphatic endothelium during the formation of FDC networks are necessary to understand the genesis and maintenance of follicles.

  17. Effects of iron status on transpulmonary transport and tissue distribution of Mn and Fe.

    PubMed

    Brain, Joseph D; Heilig, Elizabeth; Donaghey, Thomas C; Knutson, Mitchell D; Wessling-Resnick, Marianne; Molina, Ramon M

    2006-03-01

    Manganese transport into the blood can result from inhaling metal-containing particles. Intestinal manganese and iron absorption is mediated by divalent metal transporter 1 (DMT1) and is upregulated in iron deficiency. Since iron status alters absorption of Fe and Mn in the gut, we tested the hypothesis that iron status may alter pulmonary transport of these metals. DMT1 expression in the lungs was evaluated to explore its role in metal transport. The pharmacokinetics of intratracheally instilled 54Mn or 59Fe in repeatedly bled or iron oxide-exposed rats were compared with controls. Iron oxide exposure caused a reduction in pulmonary transport of 54Mn and 59Fe, and decreased uptake in other major organs. Low iron status from repeated bleeding also reduced pulmonary transport of iron but not of manganese. However, uptake of manganese in the brain and of iron in the spleen increased in bled rats. DMT1 transcripts were detected in airway epithelium, alveolar macrophages, and bronchial-associated lymphoid tissue in all rats. Focal increases were seen in particle-containing macrophages and adjacent epithelial cells, but no change was observed in bled rats. Although lung DMT1 expression did not correlate with iron status, differences in pharmacokinetics of instilled metals suggest that their potential toxicity can be modified by iron status.

  18. Differential distribution of calpain in human lymphoid cells.

    PubMed

    Deshpande, R V; Goust, J M; Banik, N L

    1993-07-01

    Calpain, a calcium-activated neutral proteinase, is ubiquitously present in human tissues. To determine if lymphoid cells implicated in pathogenesis of demyelination may harbor calpain in a functionally active form, we determined both muCalpain and mCalpain activities in human lymphoid cell lines. DEAE-cellulose and phenylsepharose column chromatography were used to isolate the enzyme from the natural inhibitor, calpastatin. Lymphocytic lines (CCRF-CEM, MOLT-3, MOLT-4, M.R.) showed predominance of muCalpain (55-80%) whereas the monocytic line (U-937) showed predominance of mCalpain (77%). Proportion and subcellular distribution of both isoforms varied among cell lines. Calpains isolated from U-937 cells degraded myelin basic protein. These results indicate that human lymphoid cells harbor functionally active calpain that can degrade myelin components in vitro. The study suggests a degradative role for calpain in demyelinating diseases.

  19. Innate lymphoid cells: the new kids on the block.

    PubMed

    Withers, David R; Mackley, Emma C; Jones, Nick D

    2015-08-01

    The purpose of this article is to review recent advances in our understanding of innate lymphoid cell function and to speculate on how these cells may become activated and influence the immune response to allogeneic tissues and cells following transplantation. Innate lymphoid cells encompass several novel cell types whose wide-ranging roles in the immune system are only now being uncovered. Through cytokine production, cross-talk with both haematopoietic and nonhaematopoietic populations and antigen presentation to T cells, these cells have been shown to be key regulators in maintaining tissue integrity, as well as initiating and then sustaining immune responses. It is now clear that innate lymphoid cells markedly contribute to immune responses and tissue repair in a number of disease contexts. Although experimental and clinical data on the behaviour of these cells following transplantation are scant, it is highly likely that innate lymphoid cells will perform similar functions in the alloimmune response following transplantation and therefore may be potential therapeutic targets for manipulation to prevent allograft rejection.

  20. Infection with 2009 H1N1 Influenza Virus Primes for Immunological Memory in Human Nose-Associated Lymphoid Tissue, Offering Cross-Reactive Immunity to H1N1 and Avian H5N1 Viruses

    PubMed Central

    Mahallawi, Waleed H.; Kasbekar, Anand V.; McCormick, Maxwell S.; Hoschler, Katja; Temperton, Nigel; Leong, Samuel C.; Beer, Helen; Ferrara, Francesca; McNamara, Paul S.

    2013-01-01

    Influenza is a highly contagious mucosal infection in the respiratory tract. The 2009 pandemic H1N1 (pH1N1) influenza virus infection resulted in substantial morbidity and mortality in humans. Little is known on whether immunological memory develops following pH1N1 infection and whether it provides protection against other virus subtypes. An enzyme-linked immunosorbent spot assay was used to analyze hemagglutinin (HA)-specific memory B cell responses after virus antigen stimulation in nose-associated lymphoid tissues (NALT) from children and adults. Individuals with serological evidence of previous exposure to pH1N1 showed significant cross-reactive HA-specific memory B cell responses to pH1N1, seasonal H1N1 (sH1N1), and avian H5N1 (aH5N1) viruses upon pH1N1 virus stimulation. pH1N1 virus antigen elicited stronger cross-reactive memory B cell responses than sH1N1 virus. Intriguingly, aH5N1 virus also activated cross-reactive memory responses to sH1N1 and pH1N1 HAs in those who had previous pH1N1 exposure, and that correlated well with the memory response stimulated by pH1N1 virus antigen. These memory B cell responses resulted in cross-reactive neutralizing antibodies against sH1N1, 1918 H1N1, and aH5N1 viruses. The 2009 pH1N1 infection appeared to have primed human host with B cell memory in NALT that offers cross-protective mucosal immunity to not only H1N1 but also aH5N1 viruses. These findings may have important implications for future vaccination strategies against influenza. It will be important to induce and/or enhance such cross-protective mucosal memory B cells. PMID:23468498

  1. The CC chemokine thymus-derived chemotactic agent 4 (TCA-4, secondary lymphoid tissue chemokine, 6Ckine, exodus-2) triggers lymphocyte function-associated antigen 1-mediated arrest of rolling T lymphocytes in peripheral lymph node high endothelial venules.

    PubMed

    Stein, J V; Rot, A; Luo, Y; Narasimhaswamy, M; Nakano, H; Gunn, M D; Matsuzawa, A; Quackenbush, E J; Dorf, M E; von Andrian, U H

    2000-01-03

    T cell homing to peripheral lymph nodes (PLNs) is defined by a multistep sequence of interactions between lymphocytes and endothelial cells in high endothelial venules (HEVs). After initial tethering and rolling via L-selectin, firm adhesion of T cells requires rapid upregulation of lymphocyte function-associated antigen 1 (LFA-1) adhesiveness by a previously unknown pathway that activates a Galpha(i)-linked receptor. Here, we used intravital microscopy of murine PLNs to study the role of thymus-derived chemotactic agent (TCA)-4 (secondary lymphoid tissue chemokine, 6Ckine, Exodus-2) in homing of adoptively transferred T cells from T-GFP mice, a transgenic strain that expresses green fluorescent protein (GFP) selectively in naive T lymphocytes (T(GFP) cells). TCA-4 was constitutively presented on the luminal surface of HEVs, where it was required for LFA-1 activation on rolling T(GFP) cells. Desensitization of the TCA-4 receptor, CC chemokine receptor 7 (CCR7), blocked T(GFP) cell adherence in wild-type HEVs, whereas desensitization to stromal cell-derived factor (SDF)-1alpha (the ligand for CXC chemokine receptor 4 [CXCR4]) did not affect T(GFP) cell behavior. TCA-4 protein was not detected on the luminal surface of PLN HEVs in plt/plt mice, which have a congenital defect in T cell homing to PLNs. Accordingly, T(GFP) cells rolled but did not arrest in plt/plt HEVs. When TCA-4 was injected intracutaneously into plt/plt mice, the chemokine entered afferent lymph vessels and accumulated in draining PLNs. 2 h after intracutaneous injection, luminal presentation of TCA-4 was detectable in a subset of HEVs, and LFA-1-mediated T(GFP) cell adhesion was restored in these vessels. We conclude that TCA-4 is both required and sufficient for LFA-1 activation on rolling T cells in PLN HEVs. This study also highlights a hitherto undocumented role for chemokines contained in afferent lymph, which may modulate leukocyte recruitment in draining PLNs.

  2. First-line response-adapted treatment with the combination of bendamustine and rituximab in patients with mucosa-associated lymphoid tissue lymphoma (MALT2008-01): a multicentre, single-arm, phase 2 trial.

    PubMed

    Salar, Antonio; Domingo-Domenech, Eva; Panizo, Carlos; Nicolás, Concepción; Bargay, Joan; Muntañola, Ana; Canales, Miguel; Bello, José Luis; Sancho, Juan Manuel; Tomás, José Francisco; Rodríguez, María José; Peñalver, Francisco Javier; Grande, Carlos; Sánchez-Blanco, José Javier; Palomera, Luis; Arranz, Reyes; Conde, Eulogio; García, Mar; García, Juan Fernando; Caballero, Dolores; Montalbán, Carlos

    2014-12-01

    No standard first-line systemic treatment for mucosa-associated lymphoid tissue (MALT) lymphoma is available. In a phase 2 study we aimed to assess the safety and activity of a response-adapted combination of bendamustine plus rituximab as upfront treatment for this type of lymphoma. In a multicentre, single-arm, non-randomised, phase 2 trial, we enrolled patients with MALT lymphoma at any site and stage and treated them with bendamustine (90 mg/m(2) on days 1 and 2) plus rituximab (375 mg/m(2) on day 1), every 4 weeks. Inclusion criteria were measurable or evaluable disease, age 18-85 years, and unequivocal active lymphoma; we also enrolled patients with MALT lymphoma arising in the stomach after failure of Helicobacter pylori eradication and primary cutaneous cases after failure of local therapies. Exclusion criteria included evidence of histological transformation, CNS involvement, and active hepatitis B or C virus or HIV infection. After three cycles, patients achieving complete response received one additional cycle (total four cycles) and those achieving partial response received three additional cycles (total six cycles). The primary endpoint was 2-year event-free survival. Analysis was by modified intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01015248. 60 patients from 19 centres in Spain were enrolled between May 27, 2009, and May 23, 2011, and received treatment; 57 patients were evaluable for the primary endpoint. Only 14 (25%) patients needed more than four cycles of treatment. After a median follow-up of 43 months (IQR 37-51), median event-free survival was not reached. Event-free survival at 2 years was 93% (95% CI 84-97) and at 4 years was 88% (95% CI 74-95). The most frequently observed grade 3-4 adverse events were haematological: lymphopenia in 20 (33%) patients, neutropenia in 12 (20%) patients, and leucopenia in three (5%) patients. Grade 3-4 febrile neutropenia or infections were reported in three (5%) and four

  3. Infection with 2009 H1N1 influenza virus primes for immunological memory in human nose-associated lymphoid tissue, offering cross-reactive immunity to H1N1 and avian H5N1 viruses.

    PubMed

    Mahallawi, Waleed H; Kasbekar, Anand V; McCormick, Maxwell S; Hoschler, Katja; Temperton, Nigel; Leong, Samuel C; Beer, Helen; Ferrara, Francesca; McNamara, Paul S; Zhang, Qibo

    2013-05-01

    Influenza is a highly contagious mucosal infection in the respiratory tract. The 2009 pandemic H1N1 (pH1N1) influenza virus infection resulted in substantial morbidity and mortality in humans. Little is known on whether immunological memory develops following pH1N1 infection and whether it provides protection against other virus subtypes. An enzyme-linked immunosorbent spot assay was used to analyze hemagglutinin (HA)-specific memory B cell responses after virus antigen stimulation in nose-associated lymphoid tissues (NALT) from children and adults. Individuals with serological evidence of previous exposure to pH1N1 showed significant cross-reactive HA-specific memory B cell responses to pH1N1, seasonal H1N1 (sH1N1), and avian H5N1 (aH5N1) viruses upon pH1N1 virus stimulation. pH1N1 virus antigen elicited stronger cross-reactive memory B cell responses than sH1N1 virus. Intriguingly, aH5N1 virus also activated cross-reactive memory responses to sH1N1 and pH1N1 HAs in those who had previous pH1N1 exposure, and that correlated well with the memory response stimulated by pH1N1 virus antigen. These memory B cell responses resulted in cross-reactive neutralizing antibodies against sH1N1, 1918 H1N1, and aH5N1 viruses. The 2009 pH1N1 infection appeared to have primed human host with B cell memory in NALT that offers cross-protective mucosal immunity to not only H1N1 but also aH5N1 viruses. These findings may have important implications for future vaccination strategies against influenza. It will be important to induce and/or enhance such cross-protective mucosal memory B cells.

  4. Antigen-Presenting Cells and Antigen Presentation in Tertiary Lymphoid Organs

    PubMed Central

    Hughes, Catherine E.; Benson, Robert A.; Bedaj, Marija; Maffia, Pasquale

    2016-01-01

    Tertiary lymphoid organs (TLOs) form in territorialized niches of peripheral tissues characterized by the presence of antigens; however, little is known about mechanism(s) of antigen handling by ectopic lymphoid structures. In this mini review, we will discuss the role of antigen-presenting cells and mechanisms of antigen presentation in TLOs, summarizing what is currently known about this facet of the formation and function of these tissues as well as identifying questions yet to be addressed. PMID:27872626

  5. Clonal immunoglobulin gene rearrangement in nodular lymphoid hyperplasia of the gastrointestinal tract associated with common variable immunodeficiency.

    PubMed

    Laszewski, M J; Kemp, J D; Goeken, J A; Mitros, F A; Platz, C E; Dick, F R

    1990-09-01

    The authors report a case of common variable immunodeficiency associated with nodular lymphoid hyperplasia of the gastrointestinal tract in which a clonal population of lymphoid cells was detected by immunophenotypic and genotypic studies on tissue obtained by colonoscopic biopsy. The patient has been followed up for more than 50 months without clinical, radiographic, or pathologic evidence of lymphoma. The significance of clonal rearrangement in the setting of immunodeficiency and the role of genotypic studies in defining lymphoid malignancy are discussed.

  6. Development and Function of Secondary and Tertiary Lymphoid Organs in the Small Intestine and the Colon

    PubMed Central

    Buettner, Manuela; Lochner, Matthias

    2016-01-01

    The immune system of the gut has evolved a number of specific lymphoid structures that contribute to homeostasis in the face of microbial colonization and food-derived antigenic challenge. These lymphoid organs encompass Peyer’s patches (PP) in the small intestine and their colonic counterparts that develop in a programed fashion before birth. In addition, the gut harbors a network of lymphoid tissues that is commonly designated as solitary intestinal lymphoid tissues (SILT). In contrast to PP, SILT develop strictly after birth and consist of a dynamic continuum of structures ranging from small cryptopatches (CP) to large, mature isolated lymphoid follicles (ILF). Although the development of PP and SILT follow similar principles, such as an early clustering of lymphoid tissue inducer (LTi) cells and the requirement for lymphotoxin beta (LTβ) receptor-mediated signaling, the formation of CP and their further maturation into ILF is associated with additional intrinsic and environmental signals. Moreover, recent data also indicate that specific differences exist in the regulation of ILF formation between the small intestine and the colon. Importantly, intestinal inflammation in both mice and humans is associated with a strong expansion of the lymphoid network in the gut. Recent experiments in mice suggest that these structures, although they resemble large, mature ILF in appearance, may represent de novo-induced tertiary lymphoid organs (TLO). While, so far, it is not clear whether intestinal TLO contribute to the exacerbation of inflammatory pathology, it has been shown that ILF provide the critical microenvironment necessary for the induction of an effective host response upon infection with enteric bacterial pathogens. Regarding the importance of ILF for intestinal immunity, interfering with the development and maturation of these lymphoid tissues may offer novel means for manipulating the immune response during intestinal infection or inflammation. PMID

  7. Detection of Quiescent Infections with Multiple Elephant Endotheliotropic Herpesviruses (EEHVs), Including EEHV2, EEHV3, EEHV6, and EEHV7, within Lymphoid Lung Nodules or Lung and Spleen Tissue Samples from Five Asymptomatic Adult African Elephants.

    PubMed

    Zong, Jian-Chao; Heaggans, Sarah Y; Long, Simon Y; Latimer, Erin M; Nofs, Sally A; Bronson, Ellen; Casares, Miguel; Fouraker, Michael D; Pearson, Virginia R; Richman, Laura K; Hayward, Gary S

    2015-12-30

    of strains of EEHV1, whose natural host has been unclear. Here, we carried out genotype analyses by partial PCR sequencing of necropsy tissue from five asymptomatic African elephants and identified multiple simultaneous infections by several different EEHV types, including high concentrations in lymphoid lung nodules. Overall, the results provide strong evidence that EEHV2, EEHV3, EEHV6, and EEHV7 represent natural ubiquitous infections in African elephants, whereas Asian elephants harbor EEHV1A, EEHV1B, EEHV4, and EEHV5. Although a single case of fatal cross-species infection by EEHV3 is known, the results do not support the previous concept that highly pathogenic EEHV1A crossed from African to Asian elephants in zoos. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  8. Lymphoid organs function as major reservoirs for human immunodeficiency virus.

    PubMed Central

    Pantaleo, G; Graziosi, C; Butini, L; Pizzo, P A; Schnittman, S M; Kotler, D P; Fauci, A S

    1991-01-01

    The total number of human immunodeficiency virus type 1 (HIV-1)-infected circulating CD4+ T lymphocytes is considered to be a reflection of the HIV burden at any given time during the course of HIV infection. However, the low frequency of HIV-infected circulating CD4+ T lymphocytes and the low level or absence of plasma viremia in the early stages of infection do not correlate with the progressive immune dysfunction characteristic of HIV infection. In this study, we have determined whether HIV-infected circulating CD4+ T lymphocytes are a correct reflection of the total pool of HIV-infected CD4+ T cells (i.e., HIV burden). To this end, HIV burden has been comparatively analyzed in peripheral blood and lymphoid tissues (lymph nodes, adenoids, and tonsils) from the same patients. The presence of HIV-1 DNA in mononuclear cells isolated simultaneously from peripheral blood and lymphoid tissues of the same patients was determined by polymerase chain reaction amplification. We found that the frequency of HIV-1-infected cells in unfractionated or sorted CD4+ cell populations isolated from lymphoid tissues was significantly higher (0.5-1 log10 unit) than the frequency in peripheral blood. Comparable results were obtained in five HIV seropositive patients in the early stages of disease and in one patient with AIDS. These results demonstrate that a heavy viral load does reside in the lymphoid organs, indicating that they may function as major reservoirs for HIV. In addition, the finding of a heavy viral load in the lymphoid organs of patients in the early stages of disease may explain the progressive depletion of CD4+ T lymphocytes and the immune dysfunction associated with the early stages of HIV infection. Images PMID:1682922

  9. The B-cell-activating factor signalling pathway is associated with Helicobacter pylori independence in gastric mucosa-associated lymphoid tissue lymphoma without t(11;18)(q21;q21).

    PubMed

    Kuo, Sung-Hsin; Tsai, Hui-Jen; Lin, Chung-Wu; Yeh, Kun-Huei; Lee, Hsiao-Wei; Wei, Ming-Feng; Shun, Chia-Tung; Wu, Ming-Shiang; Hsu, Ping-Ning; Chen, Li-Tzong; Cheng, Ann-Lii

    2017-02-01

    We previously reported that activation of the B-cell-activating factor (BAFF) pathway upregulates nuclear factor-κB (NF-κB) and induces BCL3 and BCL10 nuclear translocation in Helicobacter pylori (HP)-independent gastric diffuse large B-cell lymphoma (DLBCL) tumours with evidence of mucosa-associated lymphoid tissue (MALT). However, the significance of BAFF expression in HP independence of gastric low-grade MALT lymphomas without t(11;18)(q21;q21) remains unexplored. Sixty-four patients who underwent successful HP eradication for localized HP-positive gastric MALT lymphomas without t(11;18)(q21;q21) were studied. BAFF expression was significantly higher in the HP-independent group than in the HP-dependent group [22/26 (84.6%) versus 8/38 (21.1%); p < 0.001]. Similarly, BAFF receptor (BAFF-R) expression (p = 0.004) and nuclear BCL3 (p = 0.004), BCL10 (p < 0.001), NF-κB (p65) (p = 0.001) and NF-κB (p52) (p = 0.005) expression were closely correlated with the HP independence of these tumours. Moreover, BAFF overexpression was significantly associated with BAFF-R expression and nuclear BCL3, BCL10, NF-κB (p65) and NF-κB (p52) expression. These findings were further validated in an independent cohort, including 40 HP-dependent cases and 18 HP-independent cases of gastric MALT lymphoma without t(11;18)(q21;q21). The biological significance of BAFF signalling in t(11;18)(q21;q21)-negative lymphoma cells was further studied in two types of lymphoma B cell: OCI-Ly3 [non-germinal centre B-cell origin DLBCL without t(11;18)(q21;q21) cell line] and MA-1 [t(14;18)(q32;q21)/IGH-MALT1-positive DLBCL cell line]. In both cell lines, we found that BAFF activated the canonical NF-κB and AKT pathways, and induced the formation of BCL10-BCL3 complexes, which translocated to the nucleus. BCL10 and BCL3 nuclear translocation and NF-κB (p65) transactivation were inhibited by either LY294002 or by silencing BCL3 or BCL10 with small interfering RNA. BAFF also

  10. Innate lymphoid cells and asthma.

    PubMed

    Yu, Sanhong; Kim, Hye Young; Chang, Ya-Jen; DeKruyff, Rosemarie H; Umetsu, Dale T

    2014-04-01

    Asthma is a complex and heterogeneous disease with several phenotypes, including an allergic asthma phenotype characterized by TH2 cytokine production and associated with allergen sensitization and adaptive immunity. Asthma also includes nonallergic asthma phenotypes, such as asthma associated with exposure to air pollution, infection, or obesity, that require innate rather than adaptive immunity. These innate pathways that lead to asthma involve macrophages, neutrophils, natural killer T cells, and innate lymphoid cells, newly described cell types that produce a variety of cytokines, including IL-5 and IL-13. We review the recent data regarding innate lymphoid cells and their role in asthma. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  11. DEVELOPMENT OF CHICKEN LYMPHOID SYSTEM

    PubMed Central

    Choi, Yong Sung; Good, Robert A.

    1972-01-01

    Synthesis and secretion of Ig by chicken lymphoid cells was studied. Both spleen and bursa cells synthesize and secrete IgM and IgG whereas Ig was not detected in thymus cells. In contrast to the spleen cells which synthesize H and L chains in balanced quantities, the bursa cells synthesize and secrete free L chains. In addition to the lymphoid cells which secrete IgM or IgG, the bursa appears to contain a cell population which synthesizes nonsecretory Ig. The structure of this Ig was studied by specific serological precipitation and by SDS-acrylamide gel electrophoresis. The H chains of this nonsecretory Ig are serologically related to µ-chains and exhibit a smaller molecular weight (i.e., ∼50,000) in SDS-acrylamide gel electrophoresis than H chains of IgG and IgM synthesized by the spleen cells (i.e., ∼70,000). PMID:5022177

  12. DEVELOPMENT OF CHICKEN LYMPHOID SYSTEM

    PubMed Central

    Choi, Yong Sung; Good, Robert A.

    1972-01-01

    Development of Ig-synthesizing cells in the bursa of chick embryo was studied by immunohistochemical staining method as well as by in vitro incorporation of leucine-3H into Ig. Ig-synthesizing cells are first detected in the bursa of a 14 day old chick embryo and increase with the maturation of the embryo. Acrylamide gel analysis of leucine-3H-labeled Ig shows that synthesis of nonsecretory IgM-H0 precedes that of secretory IgM-H, reflecting an ontogenetic sequence of development of lymphoid cells synthesizing IgM. Since IgM-H0 is not secreted, we further studied biochemical differences between two heavy chains. The difference is attributable to lack of galactose attachment to H0 chains. It is proposed that during differentiation of lymphoid cells synthesizing and secreting Ig, attachment of galactose may play an obligatory role in the development of cellular capacity for Ig secretion. PMID:5033422

  13. The effect of ionizing radiation on lipid metabolism in lymphoid cells.

    PubMed

    Kolomiytseva, I K; Novoselova, E G; Kulagina, T P; Kuzin, A M

    1987-01-01

    Lipid metabolism was studied in lymphoid tissues of rats after whole body irradiation with doses producing damage of different degrees to lymphoid cells (4-10 Gy). The content of free cholesterol, cholesterol esters, and total phospholipids was determined in peripheral blood lymphocytes and thymocytes 1-2 h after exposure. Simultaneously, the rate of in vitro incorporation of 2 14C-acetate into total lipids, phospholipids, and cholesterol of lymphoid cells was estimated. It was shown that exposure of rats to ionizing radiation caused activation of lipogenesis. Cholesterol synthesis was activated after a dose of 4 Gy and decreased with increasing dose.

  14. Potential of Cells and Cytokines/Chemokines to Regulate Tertiary Lymphoid Structures in Human Diseases

    PubMed Central

    Jing, Feifeng

    2016-01-01

    Tertiary lymphoid structures (TLS) are ectopic lymphoid tissues involved in chronic inflammation, autoimmune diseases, transplant rejection and cancer. They exhibit almost all the characteristics of secondary lymphoid organs (SLO), which are associated with adaptive immune responses; as such, they contain organized B-cell follicles with germinal centers, distinct areas containing T cells and dendritic cells, high endothelial venules, and lymphatics. In this review, we briefly describe the formation of SLO, and describe the cellular subsets and molecular cues involved in the formation and maintenance of TLS. Finally, we discuss the associations of TLS with human diseases, especially autoimmune diseases, and the potential for therapeutic targeting. PMID:27799872

  15. Functional and phenotypic heterogeneity of group 3 innate lymphoid cells.

    PubMed

    Melo-Gonzalez, Felipe; Hepworth, Matthew R

    2017-03-01

    Group 3 innate lymphoid cells (ILC3), defined by expression of the transcription factor retinoid-related orphan receptor γt, play key roles in the regulation of inflammation and immunity in the gastrointestinal tract and associated lymphoid tissues. ILC3 consist largely of two major subsets, NCR(+) ILC3 and LTi-like ILC3, but also demonstrate significant plasticity and heterogeneity. Recent advances have begun to dissect the relationship between ILC3 subsets and to define distinct functional states within the intestinal tissue microenvironment. In this review we discuss the ever-expanding roles of ILC3 in the context of intestinal homeostasis, infection and inflammation - with a focus on comparing and contrasting the relative contributions of ILC3 subsets. © 2016 The Authors. Immunology published by John Wiley & Sons Ltd.

  16. Group 2 Innate Lymphoid Cells in Health and Disease

    PubMed Central

    Kim, Brian S.; Artis, David

    2015-01-01

    Group 2 innate lymphoid cells (ILC2s) play critical roles in anti-helminth immunity, airway epithelial repair, and metabolic homeostasis. Recently, these cells have also emerged as key players in the development of allergic inflammation at multiple barrier surfaces. ILC2s arise from common lymphoid progenitors in the bone marrow, are dependent on the transcription factors RORα, GATA3, and TCF-1, and produce the type 2 cytokines interleukin (IL)-4, IL-5, IL-9, and/or IL-13. The epithelial cell–derived cytokines IL-25, IL-33, and TSLP regulate the activation and effector functions of ILC2s, and recent studies suggest that their responsiveness to these cytokines and other factors may depend on their tissue environment. In this review, we focus on recent advances in our understanding of the various factors that regulate ILC2 function in the context of immunity, inflammation, and tissue repair across multiple organ systems. PMID:25573713

  17. The E-Id Protein Axis Specifies Adaptive Lymphoid Cell Identity and Suppresses Thymic Innate Lymphoid Cell Development.

    PubMed

    Miyazaki, Masaki; Miyazaki, Kazuko; Chen, Kenian; Jin, Yi; Turner, Jacob; Moore, Amanda J; Saito, Rintaro; Yoshida, Kenichi; Ogawa, Seishi; Rodewald, Hans-Reimer; Lin, Yin C; Kawamoto, Hiroshi; Murre, Cornelis

    2017-05-16

    Innate and adaptive lymphoid development is orchestrated by the activities of E proteins and their antagonist Id proteins, but how these factors regulate early T cell progenitor (ETP) and innate lymphoid cell (ILC) development remains unclear. Using multiple genetic strategies, we demonstrated that E proteins E2A and HEB acted in synergy in the thymus to establish T cell identity and to suppress the aberrant development of ILCs, including ILC2s and lymphoid-tissue-inducer-like cells. E2A and HEB orchestrated T cell fate and suppressed the ILC transcription signature by activating the expression of genes associated with Notch receptors, T cell receptor (TCR) assembly, and TCR-mediated signaling. E2A and HEB acted in ETPs to establish and maintain a T-cell-lineage-specific enhancer repertoire, including regulatory elements associated with the Notch1, Rag1, and Rag2 loci. On the basis of these and previous observations, we propose that the E-Id protein axis specifies innate and adaptive lymphoid cell fate. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Tolerance and Lymphoid Organ Structure and Function

    PubMed Central

    Burrell, Bryna E.; Ding, Yaozhong; Nakayama, Yumi; Park, Kyung-Su; Xu, Jiangnan; Yin, Na; Bromberg, Jonathan S.

    2011-01-01

    This issue of Frontiers in Immunologic Tolerance explores barriers to tolerance from a variety of views of cells, molecules, and processes of the immune system. Our laboratory has spent over a decade focused on the migration of the cells of the immune system, and dissecting the signals that determine how and where effector and suppressive regulatory T cells traffic from one site to another in order to reject or protect allografts. These studies have led us to a greater appreciation of the anatomic structure of the immune system, and the realization that the path taken by lymphocytes during the course of the immune response to implanted organs determines the final outcome. In particular, the structures, microanatomic domains, and the cells and molecules that lymphocytes encounter during their transit through blood, tissues, lymphatics, and secondary lymphoid organs are powerful determinants for whether tolerance is achieved. Thus, the understanding of complex cellular and molecular processes of tolerance will not come from “96-well plate immunology,” but from an integrated understanding of the temporal and spatial changes that occur during the response to the allograft. The study of the precise positioning and movement of cells in lymphoid organs has been difficult since it is hard to visualize cells within their three-dimensional setting; instead techniques have tended to be dominated by two-dimensional renderings, although advanced confocal and two-photon systems are changing this view. It is difficult to precisely modify key molecules and events in lymphoid organs, so that existing knockouts, transgenics, inhibitors, and activators have global and pleiotropic effects, rather than precise anatomically restricted influences. Lastly, there are no well-defined postal codes or tracking systems for leukocytes, so that while we can usually track cells from point A to point B, it is exponentially more difficult or even impossible to track them to point C and beyond

  19. Lymphoid Organ-Resident Dendritic Cells Exhibit Unique Transcriptional Fingerprints Based on Subset and Site

    PubMed Central

    Elpek, Kutlu G.; Bellemare-Pelletier, Angelique; Malhotra, Deepali; Reynoso, Erika D.; Lukacs-Kornek, Veronika; DeKruyff, Rosemarie H.; Turley, Shannon J.

    2011-01-01

    Lymphoid organ-resident DC subsets are thought to play unique roles in determining the fate of T cell responses. Recent studies focusing on a single lymphoid organ identified molecular pathways that are differentially operative in each DC subset and led to the assumption that a given DC subset would more or less exhibit the same genomic and functional profiles throughout the body. Whether the local milieu in different anatomical sites can also influence the transcriptome of DC subsets has remained largely unexplored. Here, we interrogated the transcriptional relationships between lymphoid organ-resident DC subsets from spleen, gut- and skin-draining lymph nodes, and thymus of C57BL/6 mice. For this purpose, major resident DC subsets including CD4 and CD8 DCs were sorted at high purity and gene expression profiles were compared using microarray analysis. This investigation revealed that lymphoid organ-resident DC subsets exhibit divergent genomic programs across lymphoid organs. Interestingly, we also found that transcriptional and biochemical properties of a given DC subset can differ between lymphoid organs for lymphoid organ-resident DC subsets, but not plasmacytoid DCs, suggesting that determinants of the tissue milieu program resident DCs for essential site-specific functions. PMID:21886840

  20. Histological and three dimensional organizations of lymphoid tubules in normal lymphoid organ of Penaeus monodon.

    PubMed

    Duangsuwan, Pornsawan; Phoungpetchara, Ittipon; Tinikul, Yotsawan; Poljaroen, Jaruwan; Wanichanon, Chaitip; Sobhon, Prasert

    2008-04-01

    The normal lymphoid organ of Penaeus monodon (which tested negative for WSSV and YHV) was composed of two parts: lymphoid tubules and interstitial spaces, which were permeated with haemal sinuses filled with large numbers of haemocytes. There were three permanent types of cells present in the wall of lymphoid tubules: endothelial, stromal and capsular cells. Haemocytes penetrated the endothelium of the lymphoid tubule's wall to reside among the fixed cells. The outermost layer of the lymphoid tubule was covered by a network of fibers embedded in a PAS-positive extracellular matrix, which corresponded to a basket-like network that covered all the lymphoid tubules as visualized by a scanning electron microscope (SEM). Argyrophilic reticular fibers surrounded haemal sinuses and lymphoid tubules. Together they formed the scaffold that supported the lymphoid tubule. Using vascular cast and SEM, the three dimensional structure of the subgastric artery that supplies each lobe of the lymphoid organ was reconstructed. This artery branched into highly convoluted and blind-ending terminal capillaries, each forming the lumen of a lymphoid tubule around which haemocytes and other cells aggregated to form a cuff-like wall. Stromal cells which form part of the tubular scaffold were immunostained for vimentin. Examination of the whole-mounted lymphoid organ, immunostained for vimentin, by confocal microscopy exhibited the highly branching and convoluted lymphoid tubules matching the pattern of the vascular cast observed in SEM.

  1. Artery Tertiary Lymphoid Organs: Powerhouses of Atherosclerosis Immunity

    PubMed Central

    Yin, Changjun; Mohanta, Sarajo Kumar; Srikakulapu, Prasad; Weber, Christian; Habenicht, Andreas J. R.

    2016-01-01

    Artery tertiary lymphoid organs (ATLOs) are atherosclerosis-associated lymphoid aggregates with varying degrees of complexity ranging from small T/B-cell clusters to well-structured lymph node-like though unencapsulated lymphoid tissues. ATLOs arise in the connective tissue that surrounds diseased arteries, i.e., the adventitia. ATLOs have been identified in aged atherosclerosis-prone hyperlipidemic apolipoprotein E-deficient (ApoE−/−) mice: they are organized into distinct immune cell compartments, including separate T-cell areas, activated B-cell follicles, and plasma cell niches. Analyses of ATLO immune cell subsets indicate antigen-specific T- and B-cell immune reactions within the atherosclerotic arterial wall adventitia. Moreover, ATLOs harbor innate immune cells, including a large component of inflammatory macrophages, B-1 cells, and an aberrant set of antigen-presenting cells. There is marked neoangiogenesis, irregular lymphangiogenesis, neoformation of high endothelial venules, and de novo synthesis of lymph node-like conduits. Molecular mechanisms of ATLO formation remain to be identified though media vascular smooth muscle cells may adopt features of lymphoid tissue organizer-like cells by expressing lymphorganogenic chemokines, i.e., CXCL13 and CCL21. Although these data are consistent with the view that ATLOs participate in primary T- and B-cell responses against elusive atherosclerosis-specific autoantigens, their specific protective or disease-promoting roles remain to be identified. In this review, we discuss what is currently known about ATLOs and their potential impact on atherosclerosis and make attempts to define challenges ahead. PMID:27777573

  2. Chemokine receptor CCR7 contributes to a rapid and efficient clearance of lytic murine gamma-herpes virus 68 from the lung, whereas bronchus-associated lymphoid tissue harbors virus during latency.

    PubMed

    Kocks, Jessica R; Adler, Heiko; Danzer, Heike; Hoffmann, Katharina; Jonigk, Danny; Lehmann, Ulrich; Förster, Reinhold

    2009-06-01

    Murine gamma-herpes virus 68 is a natural rodent pathogen closely related to the human gamma-herpes viruses Kaposi's sarcoma-associated herpes virus and EBV. By intranasally infecting wild-type and CCR7-deficient mice, we investigated whether CCR7 is necessary for viral clearance from the lung and the establishment of latency. We found during the lytic phase of infection that inflammation in lungs of CCR7(-/-) mice was more severe and viral load significantly higher compared with wild-type littermates. In addition, activation of T cells was delayed and clearance of the inflammation was retarded in mutant lungs, demonstrating that CCR7 is necessary for a rapid and efficient immune response. However, for the establishment of splenomegaly and latency, the presence of CCR7 was dispensable. Finally, by microdissecting BALT, we could demonstrate that these ectopic lymphoid structures are a place in the lung where virus resides during latency.

  3. Total lymphoid irradiation in the Wistar rat: technique and dosimetry

    SciTech Connect

    Hoogenhout, J.; Kazem, I.; de Jong, J.

    1983-01-01

    The technical and dosimetric aspects of total lymphoid irradiation (TLI) in the Wistar rat were evaluated as part of a set-up to develop a new model for tumor xenotransplantation. Information obtained from anatomical dissections, radionuclide imaging of the spleen, lymphography and chromolymphography was used to standardize the localization portals cut out in a lead plate. The two portals encompassed the lymphoid tissue above and below the diaphragm. A specially designed masonite phantom was used to measure the dose distribution in the simulated target volumes. Ionization chamber dosimetery, thermoluminescence dosimetry and film densitometry were used for measuring exposure and absorbed dose. Irradiation was performed with 250 kV X rays (HVL 3.1 mm Cu). The dose rate was regulated by adjusting the treatment distance. The dose inhomogeneity measured in the target volumes varied between 80-100%. The side scatter dose to non target tissues under the shielded area between the two portals ranged between 20-30%. The technique and dosimetry of total lymphoid irradiation in Wistar rats are now standardized and validated and pave the way for tumor xenotransplantation experiments.

  4. Functional Differences between Human NKp44(-) and NKp44(+) RORC(+) Innate Lymphoid Cells.

    PubMed

    Hoorweg, Kerim; Peters, Charlotte P; Cornelissen, Ferry; Aparicio-Domingo, Patricia; Papazian, Natalie; Kazemier, Geert; Mjösberg, Jenny M; Spits, Hergen; Cupedo, Tom

    2012-01-01

    Human RORC(+) lymphoid tissue inducer cells are part of a rapidly expanding family of innate lymphoid cells (ILC) that participate in innate and adaptive immune responses as well as in lymphoid tissue (re) modeling. The assessment of a potential role for innate lymphocyte-derived cytokines in human homeostasis and disease is hampered by a poor characterization of RORC(+) innate cell subsets and a lack of knowledge on the distribution of these cells in adults. Here we show that functionally distinct subsets of human RORC(+) innate lymphoid cells are enriched for secretion of IL-17a or IL-22. Both subsets have an activated phenotype and can be distinguished based on the presence or absence of the natural cytotoxicity receptor NKp44. NKp44(+) IL-22 producing cells are present in tonsils while NKp44(-) IL-17a producing cells are present in fetal developing lymph nodes. Development of human intestinal NKp44(+) ILC is a programmed event that is independent of bacterial colonization and these cells colonize the fetal intestine during the first trimester. In the adult intestine, NKp44(+) ILC are the main ILC subset producing IL-22. NKp44(-) ILC remain present throughout adulthood in peripheral non-inflamed lymph nodes as resting, non-cytokine producing cells. However, upon stimulation lymph node ILC can swiftly initiate cytokine transcription suggesting that secondary human lymphoid organs may function as a reservoir for innate lymphoid cells capable of participating in inflammatory responses.

  5. Flt3 Ligand Regulates the Development of Innate Lymphoid Cells in Fetal and Adult Mice.

    PubMed

    Baerenwaldt, Anne; von Burg, Nicole; Kreuzaler, Matthias; Sitte, Selina; Horvath, Edit; Peter, Annick; Voehringer, David; Rolink, Antonius G; Finke, Daniela

    2016-03-15

    Flt3 ligand (Flt3L) promotes survival of lymphoid progenitors in the bone marrow and differentiation of dendritic cells (DCs), but its role in regulating innate lymphoid cells (ILCs) during fetal and adult life is not understood. By using Flt3L knockout and transgenic mice, we demonstrate that Flt3L controls ILC numbers by regulating the pool of α4β7(-) and α4β7(+) lymphoid tissue inducer cell progenitors in the fetal liver and common lymphoid progenitors in the bone marrow. Deletion of flt3l severely reduced the number of fetal liver progenitors and lymphoid tissue inducer cells in the neonatal intestine, resulting in impaired development of Peyer's patches. In the adult intestine, NK cells and group 2 and 3 ILCs were severely reduced. This effect occurred independently of DCs as ILC numbers were normal in mice in which DCs were constitutively deleted. Finally, we could show that administration of Flt3L increased the number of NKp46(-) group 3 ILCs in wild-type and even in Il7(-/-) mice, which generally have reduced numbers of ILCs. Taken together, Flt3L significantly contributes to ILC and Peyer's patches development by targeting lymphoid progenitor cells during fetal and adult life. Copyright © 2016 by The American Association of Immunologists, Inc.

  6. A Stromal Cell Niche for Human and Mouse Type 3 Innate Lymphoid Cells.

    PubMed

    Hoorweg, Kerim; Narang, Priyanka; Li, Zhi; Thuery, Anne; Papazian, Natalie; Withers, David R; Coles, Mark C; Cupedo, Tom

    2015-11-01

    Adaptive immunity critically depends on the functional compartmentalization of secondary lymphoid organs. Mesenchymal stromal cells create and maintain specialized niches that support survival, activation, and expansion of T and B cells, and integrated analysis of lymphocytes and their niche has been instrumental in understanding adaptive immunity. Lymphoid organs are also home to type 3 innate lymphoid cells (ILC3), innate effector cells essential for barrier immunity. However, a specialized stromal niche for ILC3 has not been identified. A novel lineage-tracing approach now identifies a subset of murine fetal lymphoid tissue organizer cells that gives rise exclusively to adult marginal reticular cells. Moreover, both cell types are conserved from mice to humans and colocalize with ILC3 in secondary lymphoid tissues throughout life. In sum, we provide evidence that fetal stromal organizers give rise to adult marginal reticular cells and form a dedicated stromal niche for innate ILC3 in adaptive lymphoid organs. Copyright © 2015 by The American Association of Immunologists, Inc.

  7. Observations on aggregated lymphoid nodules in the cardiac glandular areas of the Bactrian camel (Camelus bactrianus).

    PubMed

    Wang, Wen-Hui

    2003-09-01

    Aggregated lymphoid nodules are an important part of the gut-associated lymphoid tissue (GALT). They are mainly distributed in the ileum and appendix of animals and humans but their distribution in the cardiac glandular area has not been reported. A study of stomach histology in the Bactrian camel has revealed that the nodules are distributed as a band-like region along the ventral wall of the stomach neck, at the beginning of the cranial enlargement and on the lesser curvature. The mucous folds are thicker in these regions than where there are no aggregated lymphoid nodules. The nodules appeared similar to ileal aggregated lymphoid nodules found in other animals and consisted of typical polymorphological lymphatic nodules arranged in a single continuous row occupying the submucosa and forming mucosal folds together with the mucous membrane. The whole mucous membrane with cardiac glands, diffuse lymphatic tissue and solitary lymphoid nodules in the lamina propria were found to cover the aggregated lymphoid nodule regions, but some nodules with a typical corona extended into the lamina propria and were covered with follicle-associated epithelium devoid of cardiac glands. These findings indicate that the stomach of the Bactrian camel possesses not only a special structure of digestion but also has characteristic immunological morphology.

  8. Treatment of intractable rheumatoid arthritis with lymphoid irradiation

    SciTech Connect

    Strober, S.; Kotzin, B.L.; Hoppe, R.T.; Slavin, S.; Gottlieb, M.; Calin, A.; Fuks, Z.; Kaplan, H.S.

    1981-01-01

    Subdiaphragmatic lymphoid radiation was used as an alternative to cytotoxic drug therapy to treat six patients with progressive erosive rheumatoid arthritis. All were previously unresponsive to conventional therapy. Radiation (4,000 rad) was given to subdiaphragmatic lymphoid tissues in fractionated doses of 150 to 250 rad each. Three of the six patients demonstrated long-lasting clinical improvement with a decrease in synovitis and morning stiffness and an increase in joint function. All six patients showed a profound depression in the peripheral blood lymphocyte count which persisted for at least six months. The irradiation was well tolerated; there have been no serious complications due to radiotherapy with follow-up ranging from 13 to 36 months. The substantial efficacy in some patients and the lack of severe toxicity in all suggests that radiotherapy deserves further study as an alternative to cytotoxic drugs in the treatment of rheumatoid arthritis.

  9. Inflammation-induced formation of fat-associated lymphoid clusters

    PubMed Central

    Bénézech, Cécile; Kruglov, Andrei A.; Loo, Yunhua; Nakamura, Kyoko; Zhang, Yang; Nayar, Saba; Jones, Lucy H.; Flores-Langarica, Adriana; McIntosh, Alistair; Marshall, Jennifer; Barone, Francesca; Besra, Gurdyal; Miles, Katherine; Allen, Judith E.; Gray, Mohini; Kollias, George; Cunningham, Adam F.; Withers, David R.; Toellner, Kai Michael; Jones, Nick D.; Veldhoen, Marc; Nedospasov, Sergei A.; McKenzie, Andrew N.J.; Caamaño, Jorge H.

    2015-01-01

    Fat-associated lymphoid clusters (FALCs) are a recently discovered type of lymphoid tissue associated with visceral fat. Here we show that distribution of FALCs was heterogeneous with the pericardium containing large numbers of these clusters. FALCs contributed to the retention of B-1 B cells in the peritoneal cavity through high expression of the chemokine CXCL13 and supported B cell proliferation and germinal center differentiation during peritoneal immune challenges. FALC formation was induced by inflammation, which triggered recruitment of myeloid cells that express tumor necrosis factor (TNF) necessary for TNF receptor-signaling in stromal cells. CD1d-restricted Natural killer T (NKT) cells were likewise required for inducible formation of FALCs. Thus, FALCs support and coordinate innate B and T cell activation during serosal immune responses. PMID:26147686

  10. Evidence that somatostatin is localized and synthesized in lymphoid organs

    SciTech Connect

    Aguila, M.C.; McCann, S.M. ); Dees, W.L.; Haensly, W.E. )

    1991-12-15

    Because several peptides originally found in the pituitary as within the central nervous system have been localized in lymphoid tissues and because somatostatin (somatotropin-release-inhibiting hormone, SRIH) can act on cells of the immune system, the authors searched for this peptide in lymphoid organs. The authors demonstrated that SRIH mRNA exists in lymphoid tissue, albeit in smaller levels that in the periventricular region of the hypothalamus, the brain region that contains the highest level of this mRNA. SRIH mRNA was found in the spleen and thymus of male rats and in the spleen, thymus, and bursa of Fabricius of the chicken. Its localization in the Bursa indicates that the peptide must be present in B lymphocytes since this is the site of origin of B lymphocytes in birds. The SRIH concentration in these lymphoid organs as determined by radioimmunoassay was greater in the thymus than in the spleen of the rat. Fluorescence immunocytochemistry revealed the presence of SRIH-positive cells in clusters inside the white pulp and more dispersed within the red pulp of the spleen of both the rat and the chicken. The thymus from these species also contained SRIH-positive cells within the medulla and around the corticomedullary junction. In the chicken, there were large cluster of SRIH-positive cells in the medullary portion of each nodule of the bursa of Fabricius. The results indicate that SRIH is synthesized and stored in cells of the immune system. SRIH may be secreted from these cells to exert paracrine actions that alter the function of immune cells in spleen and thymus.

  11. The histological characteristics of the aggregated lymphoid nodules area in abomasum of Bactrian camels (Camelus bactrianus) of different ages.

    PubMed

    Zhang, Wang-Dong; Wang, Wen-Hui; Xu, Xiao-Hong; Zhaxi, Ying-Pai; Zhang, Lin-Jiang; Qi, Shan-Shan; Li, Hang; Tan, Xue-Fen

    2012-06-30

    The aggregated lymphoid nodules area (ALNA) in abomasum of Bactrian camels is a special immune structure discovered only in Bactrian camels in recent years (2003). The anatomy research found that there was a close relationship between degree of development, anatomical characteristics and age. To further establish the relationship between histological characteristics of this special structure and animal age, 24 Alashan Bactrian camels of the following four age groups were studied: young (1-2 years), pubertal (3-5 years), middle-aged (6-16 years) and old (17-20 years). Mucosal-associated lymphoid tissue (MALT) of ALNA in abomasum was particularly observed and analyzed by histology, histochemistry and statistical methods. The results showed that the average number of lymphoid nodules in reticular mucosal folds region of ALNA in abomasum from young group to old group was in order of 26.8, 32.7, 17.6 and 7.8, and in longitudinal mucosal folds region was 20.1, 26.0, 10.3 and 5.1. The number of lymphoid nodules in the four experimental groups first increased and then decreased with increasing age (P<0.01). In young and pubertal camels lymphoid nodules were distributed evenly on both sides of the axis of mucosal folds and mostly displayed round, oval or wedge shape. The number of lymphoid nodules, follicle-associated epithelium (FAE), reticular fibers and plasmocytes in mucosal folds gradually increased from 1 to 2 years and peaked at puberty. There were up to 37 visible lymphoid nodules in a mucosal fold. However, ALNA of middle-aged and old camels gradually degenerated as aging. Lymphoid nodules were unevenly distributed on both sides of the axis of mucosal folds, which mostly displayed oval or irregular shape. Lymphoid tissue in old camels mostly existed as diffuse form. Although germinal centers of the lymphoid nodules were still obvious, the number of reticular fiber and plasmocyte and lymphoid nodules gradually decreased. The results indicated that in accord with the

  12. Is secondary lymphoid-organ chemokine (SLC/CCL21) much more than a constitutive chemokine?

    PubMed

    Serra, H M; Baena-Cagnani, C E; Eberhard, Y

    2004-11-01

    Chemokines are a superfamily of small cytokines with activities ranging from leukocyte traffick to hematopoiesis, angiogenesis, and tissue organogenesis. Secondary lymphoid-organ chemokine (SLC/CCL21) was originally reported as a chemokine constitutively expressed by stromal cells and high endothelial venules in secondary lymphoid tissues and endothelium of afferent lymphatics, directing CCR7+ cells. More recently, others and we have demonstrated that SLC/CCL21 is up-regulated in different skin inflammatory conditions. Thereafter, this molecule is much more than a constitutive chemokine, which could play a role in effector and regulatory immune functions.

  13. [Molecular targeted therapy in lymphoid leukemias].

    PubMed

    Kojima, Kensuke; Ando, Toshihiko; Kimura, Shinya

    2014-06-01

    Recent advances in the treatment of lymphoid leukemias have incorporated molecular targeted drugs (CD20-targeting rituximab and BCR-ABL tyrosine kinase inhibitors) into the traditional chemotherapeutic agents. This article reviews novel molecular targeted therapies for patients with lymphoid leukemias including acute lymphoblastic leukemia, chronic lymphocytic leukemia, hairly cell leukemia and HTLV-I-related adult T-cell leukemia. Investigational agents that will be discussed in this review include inotuzumab, blinatumomab, alemtuzumab, ofatumumab, ibrutinib, idelalisib, bafetinib, lenalidomide, ABT-199 and mogamulizumab. Novel approaches warrant continued research to improve outcomes for patients with lymphoid leukemias.

  14. The Role of TOX in the Development of Innate Lymphoid Cells.

    PubMed

    Seehus, Corey R; Kaye, Jonathan

    2015-01-01

    TOX, an evolutionarily conserved member of the HMG-box family of proteins, is essential for the development of various cells of both the innate and adaptive immune system. TOX is required for the development of CD4(+) T lineage cells in the thymus, including natural killer T and T regulatory cells, as well as development of natural killer cells and fetal lymphoid tissue inducer cells, the latter required for lymph node organogenesis. Recently, we have identified a broader role for TOX in the innate immune system, demonstrating that this nuclear protein is required for generation of bone marrow progenitors that have potential to give rise to all innate lymphoid cells. Innate lymphoid cells, classified according to transcription factor expression and cytokine secretion profiles, derive from common lymphoid progenitors in the bone marrow and require Notch signals for their development. We discuss here the role of TOX in specifying CLP toward an innate lymphoid cell fate and hypothesize a possible role for TOX in regulating Notch gene targets during innate lymphoid cell development.

  15. Maternal retinoids control type 3 innate lymphoid cells and set the offspring immunity.

    PubMed

    van de Pavert, Serge A; Ferreira, Manuela; Domingues, Rita G; Ribeiro, Hélder; Molenaar, Rosalie; Moreira-Santos, Lara; Almeida, Francisca F; Ibiza, Sales; Barbosa, Inês; Goverse, Gera; Labão-Almeida, Carlos; Godinho-Silva, Cristina; Konijn, Tanja; Schooneman, Dennis; O'Toole, Tom; Mizee, Mark R; Habani, Yasmin; Haak, Esther; Santori, Fabio R; Littman, Dan R; Schulte-Merker, Stefan; Dzierzak, Elaine; Simas, J Pedro; Mebius, Reina E; Veiga-Fernandes, Henrique

    2014-04-03

    The impact of nutritional status during fetal life on the overall health of adults has been recognized; however, dietary effects on the developing immune system are largely unknown. Development of secondary lymphoid organs occurs during embryogenesis and is considered to be developmentally programmed. Secondary lymphoid organ formation depends on a subset of type 3 innate lymphoid cells (ILC3) named lymphoid tissue inducer (LTi) cells. Here we show that mouse fetal ILC3s are controlled by cell-autonomous retinoic acid (RA) signalling in utero, which pre-sets the immune fitness in adulthood. We found that embryonic lymphoid organs contain ILC progenitors that differentiate locally into mature LTi cells. Local LTi cell differentiation was controlled by maternal retinoid intake and fetal RA signalling acting in a haematopoietic cell-autonomous manner. RA controlled LTi cell maturation upstream of the transcription factor RORγt. Accordingly, enforced expression of Rorgt restored maturation of LTi cells with impaired RA signalling, whereas RA receptors directly regulated the Rorgt locus. Finally, we established that maternal levels of dietary retinoids control the size of secondary lymphoid organs and the efficiency of immune responses in the adult offspring. Our results reveal a molecular link between maternal nutrients and the formation of immune structures required for resistance to infection in the offspring.

  16. Maternal retinoids control type 3 innate lymphoid cells and set the offspring immunity

    NASA Astrophysics Data System (ADS)

    van de Pavert, Serge A.; Ferreira, Manuela; Domingues, Rita G.; Ribeiro, Hélder; Molenaar, Rosalie; Moreira-Santos, Lara; Almeida, Francisca F.; Ibiza, Sales; Barbosa, Inês; Goverse, Gera; Labão-Almeida, Carlos; Godinho-Silva, Cristina; Konijn, Tanja; Schooneman, Dennis; O'Toole, Tom; Mizee, Mark R.; Habani, Yasmin; Haak, Esther; Santori, Fabio R.; Littman, Dan R.; Schulte-Merker, Stefan; Dzierzak, Elaine; Simas, J. Pedro; Mebius, Reina E.; Veiga-Fernandes, Henrique

    2014-04-01

    The impact of nutritional status during fetal life on the overall health of adults has been recognized; however, dietary effects on the developing immune system are largely unknown. Development of secondary lymphoid organs occurs during embryogenesis and is considered to be developmentally programmed. Secondary lymphoid organ formation depends on a subset of type 3 innate lymphoid cells (ILC3) named lymphoid tissue inducer (LTi) cells. Here we show that mouse fetal ILC3s are controlled by cell-autonomous retinoic acid (RA) signalling in utero, which pre-sets the immune fitness in adulthood. We found that embryonic lymphoid organs contain ILC progenitors that differentiate locally into mature LTi cells. Local LTi cell differentiation was controlled by maternal retinoid intake and fetal RA signalling acting in a haematopoietic cell-autonomous manner. RA controlled LTi cell maturation upstream of the transcription factor RORγt. Accordingly, enforced expression of Rorgt restored maturation of LTi cells with impaired RA signalling, whereas RA receptors directly regulated the Rorgt locus. Finally, we established that maternal levels of dietary retinoids control the size of secondary lymphoid organs and the efficiency of immune responses in the adult offspring. Our results reveal a molecular link between maternal nutrients and the formation of immune structures required for resistance to infection in the offspring.

  17. [Lymphoid neogenesis and lymphangiogenesis: two newcomers in the pathophysiology of chronic rejection].

    PubMed

    Attuil-Audenis, Valérie; Duthey, Aurélie; Patey, Natacha; Gautreau, Chantal; McGregor, Brigitte; Morelon, Emmanuel; Michel, Jean-Baptiste; Nicoletti, Antonino; Thaunat, Olivier

    2009-04-01

    Chronic rejection is one of the main causes of late allograft failure and no therapy is currently available to prevent efficiently its development. Improving the comprehension of the mechanisms involved in the pathophysiology of chronic rejection is a mandatory step to propose innovative therapies that would prolong grafts' survival. Using the rat aortic interposition model of chronic vascular rejection, we have demonstrated that the intragraft inflammatory infiltrate progressively organized itself into a functional ectopic lymphoid tissue (tertiary lymphoid organ) supporting the local synthesis of alloantibody. Thus, during chronic rejection the graft is at the same time the target and the site of elaboration of the humoral allo-immune response. This hypothesis has been confirmed in the clinical setting by the analysis of human grafts (kidneys, hearts and lungs) removed for terminal failure due to chronic rejection. This lymphoid neogenesis process, previously identified in other chronic inflammatory diseases, occurs with a strikingly high frequency in chronically rejected grafts, suggesting that an additional mechanism synergizes to initiate the development of tertiary lymphoid organs during chronic rejection. We propose that the defective lymphatic drainage of chronically rejected organs triggers lymphoid neogenesis and we discuss the complex crosstalk between lymphoid neogenesis and lymphangiogenesis that takes place during chronic rejection.

  18. Group 2 innate lymphoid cells in the lung.

    PubMed

    Drake, Li Yin; Kita, Hirohito

    2014-01-01

    As the first line of defense, innate immunity plays an important role in protecting the host against pathogens. Innate lymphoid cells (ILCs) are emerging as important effector cells in the innate immune system and the cell type that regulate immune and tissue homeostases. Group 2 ILCs (ILC2s) are a subset of ILCs and are characterized by their capacity to produce large quantities of type 2 cytokines and certain tissue growth factors. In animal models, lung ILC2s are involved in allergic airway inflammation induced by exposure to allergens even in the absence of CD4(+) T cells and are likely responsible for tissue repair and recovery after respiratory virus infection. ILC2s are also identified in various organs in humans, and the numbers are increased in mucosal tissues from patients with allergic disorders. Further investigations of this novel cell type will provide major conceptual advances in our understanding of the mechanisms of asthma and allergic diseases.

  19. Total lymphoid irradiation in alloimmunity and autoimmunity

    SciTech Connect

    Strober, S.

    1987-12-01

    Total lymphoid irradiation has been used as an immunosuppressive regimen in autoimmune disease and organ transplantation. The rationale for its use originated from studies of patients with Hodgkin disease, in whom this radiotherapy regimen was noted to induce profound and long-lasting immune suppression and yet was well tolerated, with few long-term side effects. Total lymphoid irradiation is a unique immunosuppressive regimen that produces a selective (and long-lasting) reduction in the number and function of helper T cells and certain subsets of B cells. Conventional immunosuppressive drugs show little selectivity, and their effects are short-lived. The most important aspect of total lymphoid irradiation is the potential for achieving transplantation tolerance and permanent remissions in autoimmune disease in laboratory animals. Attempts are being made to achieve similar goals in humans given total lymphoid irradiation, so that immunosuppressive drugs can be ultimately withdrawn from transplant recipients and patients with lupus nephritis. 28 references.

  20. Nfil3 is required for the development of all innate lymphoid cell subsets

    PubMed Central

    Seillet, Cyril; Rankin, Lucille C.; Groom, Joanna R.; Mielke, Lisa A.; Tellier, Julie; Chopin, Michael; Huntington, Nicholas D.

    2014-01-01

    Innate lymphoid cell (ILC) populations protect against infection and are essential for lymphoid tissue formation and tissue remodeling after damage. Nfil3 is implicated in the function of adaptive immune lineages and NK cell development, but it is not yet known if Nfil3 regulates other innate lymphoid lineages. Here, we identify that Nfil3 is essential for the development of Peyer’s patches and ILC2 and ILC3 subsets. Loss of Nfil3 selectively reduced Peyer’s patch formation and was accompanied by impaired recruitment and distribution of lymphocytes within the patches. ILC subsets exhibited high Nfil3 expression and genetic deletion of Nfil3 severely compromised the development of all subsets. Subsequently, Nfil3−/− mice were highly susceptible to disease when challenged with inflammatory or infectious agents. Thus, we demonstrate that Nfil3 is a key regulator of the development of ILC subsets essential for immune protection in the lung and gut. PMID:25092873

  1. Novel immunotherapies in lymphoid malignancies

    PubMed Central

    Batlevi, Connie Lee; Matsuki, Eri; Brentjens, Renier J.; Younes, Anas

    2016-01-01

    The success of the anti-CD20 monoclonal antibody rituximab in the treatment of lymphoid malignancies provided proof-of-principle for exploiting the immune system therapeutically. Since the FDA approval of rituximab in 1997, several novel strategies that harness the ability of T cells to target cancer cells have emerged. Reflecting on the promising clinical efficacy of these novel immunotherapy approaches, the FDA has recently granted ‘breakthrough’ designation to three novel treatments with distinct mechanisms. First, chimeric antigen receptor (CAR)-T-cell therapy is promising for the treatment of adult and paediatric relapsed and/or refractory acute lymphoblastic leukaemia (ALL). Second, blinatumomab, a bispecific T-cell engager (BiTE®) antibody, is now approved for the treatment of adults with Philadelphia-chromosome-negative relapsed and/or refractory B-precursor ALL. Finally, the monoclonal antibody nivolumab, which targets the PD-1 immune-checkpoint receptor with high affinity, is used for the treatment of Hodgkin lymphoma following treatment failure with autologous-stem-cell transplantation and brentuximab vedotin. Herein, we review the background and development of these three distinct immunotherapy platforms, address the scientific advances in understanding the mechanism of action of each therapy, and assess the current clinical knowledge of their efficacy and safety. We also discuss future strategies to improve these immunotherapies through enhanced engineering, biomarker selection, and mechanism-based combination regimens. PMID:26525683

  2. Total lymphoid irradiation and discordant cardiac xenografts

    SciTech Connect

    Kaplan, E.; Dresdale, A.R.; Diehl, J.T.; Katzen, N.A.; Aronovitz, M.J.; Konstam, M.A.; Payne, D.D.; Cleveland, R.J. )

    1990-01-01

    Total lymphoid irradiation can prolong concordant cardiac xenografts. The effects of total lymphoid irradiation in a discordant xenograft model (guinea pig to rat) were studied with and without adjuvant pharmacologic immunosuppression. Inbred Lewis rats were randomly allocated to one of four groups. Group 1 (n = 6) served as a control group and rats received no immunosuppression. Group 2 (n = 5) received triple-drug therapy that consisted of intraperitoneal azathioprine (2 mg/kg), cyclosporine (20 mg/kg), and methylprednisolone (1 mg/kg) for 1 week before transplantation. Group 3 animals (n = 5) received 15 Gy of total lymphoid irradiation in 12 divided doses over a 3-week period. Group 4 (n = 6) received both triple-drug therapy and total lymphoid irradiation as described for groups 2 and 3. Complement-dependent cytotoxicity assay was performed to determine if a correlation between complement-dependent cytotoxicity and rejection-free interval existed. Rejection was defined as cessation of graft pulsation and was confirmed by histologic test results. Only groups 1 and 2 showed a difference in survival (group 1, 6.9 +/- 1.0 minutes; group 2, 14.2 +/- 2.7 minutes, p = 0.02). Although total lymphoid irradiation did decrease complement-dependent cytotoxicity, linear regression revealed no correlation between complement-dependent cytotoxicity and graft survival (coefficient of correlation, 0.30). Unlike concordant cardiac xenografts, total lymphoid irradiation with or without triple-drug therapy does not prolong graft survival.

  3. Isolation and characterization of mouse innate lymphoid cells.

    PubMed

    Halim, Timotheus Y F; Takei, Fumio

    2014-08-01

    Innate lymphoid cells (ILCs) are rare populations of cytokine-producing lymphocytes and are divided into three groups, namely ILC1, ILC2, and ILC3, based on the cytokines that they produce. They comprise less than 1% of lymphocytes in mucosal tissues and express no unique cell surface markers. Therefore, they can only be identified by combinations of multiple cell surface markers and further characterized by cytokine production in vitro. Thus, multicolor flow cytometry is the only reliable method to purify and characterize ILCs. Here we describe the methods for cell preparation, flow cytometric analysis, and purification of murine ILC2 and ILC3. Copyright © 2014 John Wiley & Sons, Inc.

  4. Structural Changes in Large Intestinal Aggregated Lymphoid Follicles in Wistar Rats During Postnatal Ontogeny.

    PubMed

    Tikhonov, E A

    2015-09-01

    Quantitative evaluation of aggregated lymphoid follicles in various compartments of the large intestine was carried out in Wistar rats of different age: newborn (3-4 days), prepubertal (20-30 days), adult (2-3 months), and old (16-18 months). No aggregated lymphoid tissue was detected in the large intestinal mucosa of newborn animals. The cecum of prepubertal, adult, and old animals contained solitary patches with 7-9 follicles. Higher percentage of aggregated lymphoid tissue, associated with colonic mucosa, was explained by enlargement of the lymphoid patch area and of the number of solitary lymphoid follicles during the postnatal ontogenesis. The mean area of a patch in the distal part of the colon in prepubertal, adult, and old animals was 3.2, 2.5, and 2.2 times larger than in the medial part of the intestine, the number of follicles per patch was 2.8, 2.8, and 2.5 times higher, respectively. The differences were significant only for the two younger groups.

  5. The Yin and Yang of Innate Lymphoid Cells in Cancer.

    PubMed

    Carrega, Paolo; Campana, Stefania; Bonaccorsi, Irene; Ferlazzo, Guido

    2016-11-01

    The recent appreciation of novel subsets of innate lymphoid cells (ILCs) as important regulators of tissue homeostasis, inflammation and repair, raise questions regarding the presence and role of these cells in cancer tissues. In addition to natural killer and fetal lymphoid tissue inducer (LTi) cells, the ILC family comprises non-cytolytic, cytokine-producing cells that are classified into ILC1, ILC2 and ILC3 based on phenotypic and functional characteristics. Differently from natural killer cells, which are the prototypical members of ILC1 and whose role in tumors is better established, the involvement of other ILC subsets in cancer progression or resistance is still fuzzy and in several instances controversial, since current studies indicate both context-dependent beneficial or pathogenic effects. Here, we review the current knowledge regarding the involvement of these novel ILC subsets in the context of tumor immunology, highlighting how ILC subsets might behave either as friends or foes. Copyright © 2016 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  6. Max D. Cooper and the delineation of two lymphoid lineages in the adaptive immune system.

    PubMed

    Ribatti, Domenico

    2014-11-01

    This article outlines the fundamental contribution of Max D. Cooper to the analysis of the role of the thymus and of the bursa of Fabricius in the development of immunologic competence both before and after birth, placing a new scientific paradigm in the definition of the ontogeny of the lymphoid tissues.

  7. Emerging concepts and future challenges in innate lymphoid cell biology

    PubMed Central

    Artis, David

    2016-01-01

    Innate lymphoid cells (ILCs) are innate immune cells that are ubiquitously distributed in lymphoid and nonlymphoid tissues and enriched at mucosal and barrier surfaces. Three major ILC subsets are recognized in mice and humans. Each of these subsets interacts with innate and adaptive immune cells and integrates cues from the epithelium, the microbiota, and pathogens to regulate inflammation, immunity, tissue repair, and metabolic homeostasis. Although intense study has elucidated many aspects of ILC development, phenotype, and function, numerous challenges remain in the field of ILC biology. In particular, recent work has highlighted key new questions regarding how these cells communicate with their environment and other cell types during health and disease. This review summarizes new findings in this rapidly developing field that showcase the critical role ILCs play in directing immune responses through their ability to interact with a variety of hematopoietic and nonhematopoietic cells. In addition, we define remaining challenges and emerging questions facing the field. Finally, this review discusses the potential application of basic studies of ILC biology to the development of new treatments for human patients with inflammatory and infectious diseases in which ILCs play a role. PMID:27811053

  8. Evidence for Adaptive Evolution at the Divergence Between Lymphoid and Brain HIV-1 nef Genes

    PubMed Central

    Olivieri, Kevin C.; Agopian, Kristin A.; Mukerji, Joya

    2010-01-01

    Abstract Human immunodeficiency virus type 1 (HIV) infection of the central nervous system frequently causes HIV-associated neurocognitive disorders (HAND). The role of HIV Nef and other accessory proteins in HAND pathogenesis is unclear. To determine whether HIV nef undergoes adaptive selection in brain, we cloned 100 nef sequences (n = 30 brain and n = 70 lymphoid) from four patients with AIDS and HIV-associated dementia (HAD). Normalized nonsynonymous substitutions were more frequent at the divergence of lymphoid and brain sequences, indicating stronger adaptive selection in brain compared to lymphoid tissue. Brain-specific nonsynonymous substitutions were found within an NH3-terminal CTL epitope, the PACS1 binding motif, or positions predicted to be important for activation of the myeloid-restricted Src family tyrosine kinase Hck. These results suggest that adaptive selection of HIV nef in brain may reflect altered requirements for efficient replication in macrophages and brain-specific immune selection pressures. PMID:20377428

  9. Autotaxin, a lysophosphatidic acid-producing ectoenzyme, promotes lymphocyte entry into secondary lymphoid organs

    PubMed Central

    Kanda, Hidenobu; Newton, Rebecca; Klein, Russell; Morita, Yuka; Gunn, Michael D.; Rosen, Steven D.

    2009-01-01

    The extracellular lysophospholipase D, autotaxin (ATX), and its product lysophosphatidic acid (LPA) have diverse roles in development and cancer, but little is known about functions in the immune system. We found that ATX was highly expressed in high endothelial venules (HEVs) of lymphoid organs and was secreted. Chemokine-activated lymphocytes expressed enhanced receptors for ATX, providing a mechanism to target the secreted ATX onto lymphocytes undergoing recruitment. LPA induced chemokinesis in T-cells. Intravenous injection of enzymatically inactive ATX attenuated homing of T-cells to lymphoid tissues, likely by competing with endogenous ATX and exerting a dominant-negative effect. Our results support a novel and general step in the homing cascade, in which the ectoenzyme ATX facilitates lymphocyte entry into lymphoid organs. PMID:18327261

  10. A Progenitor Cell Expressing Transcription Factor RORγt Generates All Human Innate Lymphoid Cell Subsets.

    PubMed

    Scoville, Steven D; Mundy-Bosse, Bethany L; Zhang, Michael H; Chen, Li; Zhang, Xiaoli; Keller, Karen A; Hughes, Tiffany; Chen, Luxi; Cheng, Stephanie; Bergin, Stephen M; Mao, Hsiaoyin C; McClory, Susan; Yu, Jianhua; Carson, William E; Caligiuri, Michael A; Freud, Aharon G

    2016-05-17

    The current model of murine innate lymphoid cell (ILC) development holds that mouse ILCs are derived downstream of the common lymphoid progenitor through lineage-restricted progenitors. However, corresponding lineage-restricted progenitors in humans have yet to be discovered. Here we identified a progenitor population in human secondary lymphoid tissues (SLTs) that expressed the transcription factor RORγt and was unique in its ability to generate all known ILC subsets, including natural killer (NK) cells, but not other leukocyte populations. In contrast to murine fate-mapping data, which indicate that only ILC3s express Rorγt, these human progenitor cells as well as human peripheral blood NK cells and all mature ILC populations expressed RORγt. Thus, all human ILCs can be generated through an RORγt(+) developmental pathway from a common progenitor in SLTs. These findings help establish the developmental signals and pathways involved in human ILC development.

  11. Homeostatic migration and distribution of innate immune cells in primary and secondary lymphoid organs with ageing.

    PubMed

    Nikolich-Žugich, J; Davies, J S

    2017-03-01

    Ageing of the innate and adaptive immune system, collectively termed immune senescence, is a complex process. One method to understand the components of ageing involves dissociating the effects of ageing on the cells of the immune system, on the microenvironment in lymphoid organs and tissues where immune cells reside and on the circulating factors that interact with both immune cells and their microenvironment. Heterochronic parabiosis, a surgical union of two organisms of disparate ages, is ideal for this type of study, as it has the power to dissociate the age of the cell and the age of the microenvironment into which the cell resides or is migrating. So far, however, it has been used sparingly to study immune ageing. Here we review the limited literature on homeostatic innate immune cell trafficking in ageing in the absence of chronic inflammation. We also review our own recent data on trafficking of innate immune subsets between primary and secondary lymphoid organs in heterochronic parabiosis. We found no systemic bias in retention or acceptance of neutrophils, macrophages, dendritic cells or natural killer cells with ageing in primary and secondary lymphoid organs. We conclude that these four innate immune cell types migrate to and populate lymphoid organs (peripheral lymph nodes, spleen and bone marrow), regardless of their own age and of the age of lymphoid organs. © 2017 British Society for Immunology.

  12. Group 3 innate lymphoid cells (ILC3s): Origin, differentiation, and plasticity in humans and mice.

    PubMed

    Montaldo, Elisa; Juelke, Kerstin; Romagnani, Chiara

    2015-08-01

    Since their discovery, innate lymphoid cells (ILCs) have been the subject of intense research. As their name implies, ILCs are innate cells of lymphoid origin, and can be grouped into subsets based on their cytotoxic activity, cytokine profile, and the transcriptional requirements during ILC differentiation. The main ILC groups are "killer" ILCs, comprising NK cells, and "helper-like" ILCs (including ILC1s, ILC2s, and ILC3s). This review examines the origin, differentiation stages, and plasticity of murine and human ILC3s. ILC3s express the retinoic acid receptor (RAR) related orphan receptor RORγt and the signature cytokines IL-22 and IL-17. Fetal ILC3s or lymphoid tissue inducer cells are required for lymphoid organogenesis, while postnatally developing ILC3s are important for the generation of intestinal cryptopatches and isolated lymphoid follicles as well as for the defence against pathogens and epithelial homeostasis. Here, we discuss the transcription factors and exogenous signals (including cytokines, nutrients and cell-to-cell interaction) that drive ILC3 lineage commitment and acquisition of their distinctive effector program. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Human secondary lymphoid organs typically contain polyclonally-activated proliferating regulatory T cells.

    PubMed

    Peters, Jorieke H; Koenen, Hans J P M; Fasse, Esther; Tijssen, Henk J; Ijzermans, Jan N M; Groenen, Patricia J T A; Schaap, Nicolaas P M; Kwekkeboom, Jaap; Joosten, Irma

    2013-09-26

    Immunomodulating regulatory T-cell (Treg) therapy is a promising strategy in autoimmunity and transplantation. However, to achieve full clinical efficacy, better understanding of in vivo human Treg biology is warranted. Here, we demonstrate that in contrast to blood and bone marrow Tregs, which showed a resting phenotype, the majority of CD4(pos)CD25(pos)CD127(neg)FoxP3(pos) Tregs in secondary lymphoid organs were proliferating activated CD69(pos)CD45RA(neg) cells with a hyperdemethylated FOXP3 gene and a broad T-cell receptor-Vβ repertoire, implying polyclonal activation. Activated CD69(pos) Tregs were distributed over both T-cell and B-cell areas, distant from Aire(pos) and CD11c(pos) cells. In contrast to the anergic peripheral blood Tregs, lymphoid organ Tregs had significant ex vivo proliferative capacity and produced cytokines like interleukin-2, while revealing similar suppressive potential. Also, next to Treg-expressing chemokine receptors important for a prolonged stay in lymphoid organs, a significant part of the cells expressed peripheral tissue-associated, functional homing markers. In conclusion, our data suggest that human secondary lymphoid organs aid in the maintenance and regulation of Treg function and homeostasis. This knowledge may be exploited for further optimization of Treg immunotherapy, for example, by ex vivo selection of Tregs with capacity to migrate to lymphoid organs providing an in vivo platform for further Treg expansion.

  14. Comparative genomics analysis of mononuclear phagocyte subsets confirms homology between lymphoid tissue-resident and dermal XCR1(+) DCs in mouse and human and distinguishes them from Langerhans cells.

    PubMed

    Carpentier, Sabrina; Vu Manh, Thien-Phong; Chelbi, Rabie; Henri, Sandrine; Malissen, Bernard; Haniffa, Muzlifah; Ginhoux, Florent; Dalod, Marc

    2016-05-01

    Dendritic cells (DC) are mononuclear phagocytes which exhibit a branching (dendritic) morphology and excel at naïve T cell activation. DC encompass several subsets initially identified by their expression of cell surface molecules and later shown to possess distinct functions. DC subset differentiation is orchestrated by transcription factors, growth factors and cytokines. Identifying DC subsets is challenging as very few cell surface molecules are uniquely expressed on any one of these cell populations. There is no standard consensus to identify mononuclear phagocyte subsets; varying antigens are employed depending on the tissue and animal species studied and between laboratories. This has led to confusion in how to accurately define and classify DCs across tissues and between species. Here we report a comparative genomics strategy that enables universal definition of DC and other mononuclear phagocyte subsets across species. We performed a meta-analysis of several public datasets of human and mouse mononuclear phagocyte subsets isolated from blood, spleen, skin or cutaneous lymph nodes, including by using a novel and user friendly software, BubbleGUM, which generates and integrates gene signatures for high throughput gene set enrichment analysis. This analysis demonstrates the equivalence between human and mouse skin XCR1(+) DCs, and between mouse and human Langerhans cells. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  15. Comparative genomics analysis of mononuclear phagocyte subsets confirms homology between lymphoid tissue-resident and dermal XCR1+ DCs in mouse and human and distinguishes them from Langerhans cells

    PubMed Central

    Carpentier, Sabrina; Vu Manh, Thien-Phong; Chelbi, Rabie; Henri, Sandrine; Malissen, Bernard; Haniffa, Muzlifah; Ginhoux, Florent; Dalod, Marc

    2016-01-01

    Dendritic cells (DC) are mononuclear phagocytes which exhibit a branching (dendritic) morphology and excel at naïve T cell activation. DC encompass several subsets initially identified by their expression of cell surface molecules and later shown to possess distinct functions. DC subset differentiation is orchestrated by transcription factors, growth factors and cytokines. Identifying DC subsets is challenging as very few cell surface molecules are uniquely expressed on any one of these cell populations. There is no standard consensus to identify mononuclear phagocyte subsets; varying antigens are employed depending on the tissue and animal species studied and between laboratories. This has led to confusion in how to accurately define and classify DCs across tissues and between species. Here we report a comparative genomics strategy that enables universal definition of DC and other mononuclear phagocyte subsets across species. We performed a meta-analysis of several public datasets of human and mouse mononuclear phagocyte subsets isolated from blood, spleen, skin or cutaneous lymph nodes, including by using a novel and user friendly software, BubbleGUM, which generates and integrates gene signatures for high throughput gene set enrichment analysis. This analysis demonstrates the equivalence between human and mouse skin XCR1+ DCs, and between mouse and human Langerhans cells. PMID:26966045

  16. The evolution of innate lymphoid cells.

    PubMed

    Vivier, Eric; van de Pavert, Serge A; Cooper, Max D; Belz, Gabrielle T

    2016-06-21

    Innate lymphoid cells (ILCs) are the most recently discovered group of immune cells. Understanding their biology poses many challenges. We discuss here the current knowledge on the appearance of ILC subsets during evolution and propose how the connection between ILCs and T cells contributes to the robustness of immunity and hence to the fitness of the hosts.

  17. The evolution of innate lymphoid cells

    PubMed Central

    Vivier, Eric; van de Pavert, Serge A; Cooper, Max D; Belz, Gabrielle T

    2017-01-01

    Innate lymphoid cells (ILCs) are the most recently discovered group of immune cells. Understanding their biology poses many challenges. We discuss here the current knowledge on the appearance of ILC subsets during evolution and propose how the connection between ILCs and T cells contributes to the robustness of immunity and hence to the fitness of the hosts. PMID:27328009

  18. The Role of Lymphoid Neogenesis in Allografts

    PubMed Central

    Hsao, Hsi-Min; Li, Wenjun; Gelman, Andrew E.; Krupnick, Alexander S.; Kreisel, Daniel

    2016-01-01

    De novo induction of organized lymphoid aggregates at non-lymphoid sites has been observed in many chronic inflammatory conditions where foreign antigens such as infectious agents, auto- or alloantigens, persist. The prevailing opinion in the field of transplantation is that lymphoid neogenesis within allografts is detrimental to the establishment of immune tolerance. These structures, commonly referred to as tertiary lymphoid organs (TLOs), are thought to contribute to graft rejection by generating and propagating local alloimmune responses. However, recent studies have shown that TLOs rich in regulatory Foxp3+ cells are present in long term accepting allografts. The notion that TLOs can contribute to the local downregulation of immune responses has been corroborated in other chronic inflammation models. These findings suggest that contrary to previous suggestions that the induction of TLOs in allografts is necessarily harmful, the induction of “tolerogenic” TLOs may prove advantageous. In this review, we discuss our current understanding of how TLOs are induced and how they regulate immune responses with a particular focus on alloimmunity. PMID:26614734

  19. Improved Culture Medium (TiKa) for Mycobacterium avium Subspecies Paratuberculosis (MAP) Matches qPCR Sensitivity and Reveals Significant Proportions of Non-viable MAP in Lymphoid Tissue of Vaccinated MAP Challenged Animals

    PubMed Central

    Bull, Tim J.; Munshi, Tulika; Mikkelsen, Heidi; Hartmann, Sofie B.; Sørensen, Maria R.; Garcia, Joanna S.; Lopez-Perez, Paula M.; Hofmann, Sven; Hilpert, Kai; Jungersen, Gregers

    2017-01-01

    The quantitative detection of viable pathogen load is an important tool in determining the degree of infection in animals and contamination of foodstuffs. Current conventional culture methods are limited in their ability to determine these levels in Mycobacterium avium subspecies paratuberculosis (MAP) due to slow growth, clumping and low recoverability issues. The principle goal of this study was to evaluate a novel culturing process (TiKa) with unique ability to stimulate MAP growth from low sample loads and dilutions. We demonstrate it was able to stimulate a mean 29-fold increase in recoverability and an improved sensitivity of up to three logs when compared with conventional culture. Using TiKa culture, MAP clumping was minimal and produced visible colonies in half the time required by standard culture methods. Parallel quantitative evaluation of the TiKa culture approach and qPCR on MAP loads in tissue and gut mucosal samples from a MAP vaccine-challenge study, showed good correlations between colony counts (cfu) and qPCR derived genome equivalents (Geq) over a large range of loads with a 30% greater sensitivity for TiKa culture approach at low loads (two logs). Furthermore, the relative fold changes in Geq and cfu from the TiKa culture approach suggests that non-mucosal tissue loads from MAP infected animals contained a reduced proportion of non-viable MAP (mean 19-fold) which was reduced significantly further (mean 190-fold) in vaccinated “reactor” calves. This study shows TiKa culture equates well with qPCR and provides important evidence that accuracy in estimating viable MAP load using DNA tests alone may vary significantly between samples of mucosal and lymphatic origin. PMID:28101082

  20. Improved Culture Medium (TiKa) for Mycobacterium avium Subspecies Paratuberculosis (MAP) Matches qPCR Sensitivity and Reveals Significant Proportions of Non-viable MAP in Lymphoid Tissue of Vaccinated MAP Challenged Animals.

    PubMed

    Bull, Tim J; Munshi, Tulika; Mikkelsen, Heidi; Hartmann, Sofie B; Sørensen, Maria R; Garcia, Joanna S; Lopez-Perez, Paula M; Hofmann, Sven; Hilpert, Kai; Jungersen, Gregers

    2016-01-01

    The quantitative detection of viable pathogen load is an important tool in determining the degree of infection in animals and contamination of foodstuffs. Current conventional culture methods are limited in their ability to determine these levels in Mycobacterium avium subspecies paratuberculosis (MAP) due to slow growth, clumping and low recoverability issues. The principle goal of this study was to evaluate a novel culturing process (TiKa) with unique ability to stimulate MAP growth from low sample loads and dilutions. We demonstrate it was able to stimulate a mean 29-fold increase in recoverability and an improved sensitivity of up to three logs when compared with conventional culture. Using TiKa culture, MAP clumping was minimal and produced visible colonies in half the time required by standard culture methods. Parallel quantitative evaluation of the TiKa culture approach and qPCR on MAP loads in tissue and gut mucosal samples from a MAP vaccine-challenge study, showed good correlations between colony counts (cfu) and qPCR derived genome equivalents (Geq) over a large range of loads with a 30% greater sensitivity for TiKa culture approach at low loads (two logs). Furthermore, the relative fold changes in Geq and cfu from the TiKa culture approach suggests that non-mucosal tissue loads from MAP infected animals contained a reduced proportion of non-viable MAP (mean 19-fold) which was reduced significantly further (mean 190-fold) in vaccinated "reactor" calves. This study shows TiKa culture equates well with qPCR and provides important evidence that accuracy in estimating viable MAP load using DNA tests alone may vary significantly between samples of mucosal and lymphatic origin.

  1. Human innate lymphoid cells (ILCs) in filarial infections.

    PubMed

    Bonne-Année, S; Nutman, T B

    2017-05-15

    Filarial infections are characteristically chronic and can cause debilitating diseases governed by parasite-induced innate and adaptive immune responses. Filarial parasites traverse or establish niches in the skin (migrating infective larvae), in nonmucosal tissues (adult parasite niche) and in the blood or skin (circulating microfilariae) where they intersect with the host immune response. While several studies have demonstrated that filarial parasites and their antigens can modulate myeloid cells (monocyte, macrophage and dendritic cell subsets), T- and B-lymphocytes and skin resident cell populations, the role of innate lymphoid cells during filarial infections has only recently emerged. Despite the identification and characterization of innate lymphoid cells (ILCs) in murine helminth infections, little is actually known about the role of human ILCs during parasitic infections. The focus of this review will be to highlight the composition of ILCs in the skin, lymphatics and blood; where the host-parasite interaction is well-defined and to examine the role of ILCs during filarial infections. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

  2. Innate lymphoid cells in graft-versus-host disease.

    PubMed

    Konya, V; Mjösberg, J

    2015-11-01

    Innate lymphoid cells (ILC) are lymphocytes lacking rearranged antigen receptors such as those expressed by T and B cells. ILC are important effector and regulatory cells of the innate immune system, controlling lymphoid organogenesis, tissue inflammation, and homeostasis. The family of ILC consists of cytotoxic NK cells and the more recently described noncytotoxic group 1, 2, and 3 ILC. The classification of noncytotoxic ILC-in many aspects-mirrors that of T helper cells, which is based on the expression of master transcription factors and signature cytokines specific for each subset. The IL-22 producing RORγt(+) ILC3 subset was recently found to be critical in the prevention of intestinal graft-versus-host disease (GVHD) following allogeneic hematopoietic cell transplantation (HCT) via strengthening the intestinal mucosal barrier. In this review, we summarize the current view of the immunological functions of human noncytotoxic ILC subsets and discuss the potentially beneficial features of IL-22 producing ILC3 in improving allo-HCT efficacy by attenuating susceptibility to GVHD. In addition, we explore the possibility of other ILC subsets playing a role in GVHD. © 2015 The Authors. American Journal of Transplantation published by Wiley Periodicals, Inc. on behalf of American Society of Transplant Surgeons.

  3. Persistence and responsiveness of immunologic memory in the absence of secondary lymphoid organs.

    PubMed

    Moyron-Quiroz, Juan E; Rangel-Moreno, Javier; Hartson, Louise; Kusser, Kim; Tighe, Michael P; Klonowski, Kimberly D; Lefrançois, Leo; Cauley, Linda S; Harmsen, Allen G; Lund, Frances E; Randall, Troy D

    2006-10-01

    Secondary lymphoid organs (SLOs) promote primary immune responses by recruiting naive lymphocytes and activated APCs. However, their role in the persistence or responsiveness of memory lymphocytes is unclear. We tested whether memory cells were maintained and could respond to challenge in the absence of SLOs. We found that influenza-specific CD8 cells in the lung acquired a memory phenotype, underwent homeostatic proliferation, recirculated through nonlymphoid tissues, and responded to and cleared a challenge infection in the complete absence of SLOs. Similarly, influenza-specific virus-neutralizing antibody was generated and maintained in the absence of SLOs. Inducible bronchus-associated lymphoid tissue (iBALT) was also formed in the lungs of previously infected mice and may provide a niche for the maintenance of memory cells at the local level. These data show that SLOs are dispensable for the maintenance of immunologic memory and directly demonstrate the utility of local tissues, such as iBALT, in secondary immune responses.

  4. Elevated autoantibody content in rheumatoid arthritis synovia with lymphoid aggregates and the effect of rituximab.

    PubMed

    Rosengren, Sanna; Wei, Nathan; Kalunian, Kenneth C; Zvaifler, Nathan J; Kavanaugh, Arthur; Boyle, David L

    2008-01-01

    The purpose of this study was to quantitatively evaluate the contribution of synovial lymphoid aggregates to autoantibody (rheumatoid factor [RF] and anti-cyclic citrullinated peptide [anti-CCP]) and total immunoglobulin (IgG and IgM) production in rheumatoid arthritis (RA) patients and the effect thereon of the B-cell-depleting antibody, rituximab, in the ARISE (Assessment of Rituximab's Immunomodulatory Synovial Effects) trial. Autoantibodies as well as total IgM and IgG were quantified by enzyme-linked immunosorbent assay in extracts of synovial tissues and matched serum from patients with RA or osteoarthritis (OA). Synovial biopsies and serum were obtained at baseline and 8 weeks following rituximab therapy in 14 RA patients. A synovial/serum index (SSI) was calculated as the ratio of synovial to serum antibody/albumin, with values above 1 representing synovial enrichment. Lymphoid aggregates were evaluated histologically. Anti-CCP IgG, but not RF-IgM, was significantly enriched in RA synovia compared with serum. Total IgM and IgG were also enriched in RA, but not in OA. SSI correlated significantly with mRNA content for both IgM and IgG, demonstrating that it reflected synovial immunoglobulin production. RA synovia with lymphocyte aggregates contained significantly elevated RF-IgM and anti-CCP IgG compared with tissues with diffuse lymphoid infiltration. Rituximab treatment did not affect synovial autoantibody or total immunoglobulin SSI overall. However, in aggregate-containing tissues, rituximab significantly reduced total IgM and IgG SSI as well as IgM and IgG1 mRNA. Surprisingly, RF-IgM and anti-CCP IgG SSIs were unchanged by rituximab in aggregate-containing synovia. Combined with earlier observations that synovial lymphoid aggregates are unaltered by rituximab treatment, these data suggest that lymphoid aggregates may provide a protective niche for autoantibody-producing cells.

  5. Excessive reactive lymphoid hyperplasia in a child with persistent obstructive sleep apnea despite previous tonsillectomy and adenoidectomy.

    PubMed

    Acar, Gül Özbilen; Cansz, Harun; Duman, Cihan; Öz, Büge; Ciğercioğullar, Engin

    2011-07-01

    Both lingual tonsil and adenoid are the lymphoid tissue members of Waldeyer ring. Enlargement of the lingual tonsil and adenoid occurs in children with persistent obstructive sleep apnea despite previous tonsillectomy and adenoidectomy relatively frequently.In this article, we present a case with upper airway obstruction and infection findings because of excessive lingual tonsil and adenoid tissue hyperplasia and, additionally, bilateral multiple cervical lymphadenopathies. The patient had had tonsillectomy and adenoidectomy 8 years ago. Etiopathogenetic mechanisms, clinical, radiologic, histopathologic aspects, and surgical therapeutic options for obstructive sleep apnea related to excessive reactive lymphoid hyperplasia in children are discussed reviewing the literature.

  6. The Cc Chemokine Thymus-Derived Chemotactic Agent 4 (Tca-4, Secondary Lymphoid Tissue Chemokine, 6ckine, Exodus-2) Triggers Lymphocyte Function–Associated Antigen 1–Mediated Arrest of Rolling T Lymphocytes in Peripheral Lymph Node High Endothelial Venules

    PubMed Central

    Stein, Jens V.; Rot, Antal; Luo, Yi; Narasimhaswamy, Manjunath; Nakano, Hideki; Gunn, Michael D.; Matsuzawa, Akio; Quackenbush, Elizabeth J.; Dorf, Martin E.; von Andrian, Ulrich H.

    2000-01-01

    T cell homing to peripheral lymph nodes (PLNs) is defined by a multistep sequence of interactions between lymphocytes and endothelial cells in high endothelial venules (HEVs). After initial tethering and rolling via L-selectin, firm adhesion of T cells requires rapid upregulation of lymphocyte function–associated antigen 1 (LFA-1) adhesiveness by a previously unknown pathway that activates a Gαi-linked receptor. Here, we used intravital microscopy of murine PLNs to study the role of thymus-derived chemotactic agent (TCA)-4 (secondary lymphoid tissue chemokine, 6Ckine, Exodus-2) in homing of adoptively transferred T cells from T-GFP mice, a transgenic strain that expresses green fluorescent protein (GFP) selectively in naive T lymphocytes (TGFP cells). TCA-4 was constitutively presented on the luminal surface of HEVs, where it was required for LFA-1 activation on rolling TGFP cells. Desensitization of the TCA-4 receptor, CC chemokine receptor 7 (CCR7), blocked TGFP cell adherence in wild-type HEVs, whereas desensitization to stromal cell–derived factor (SDF)-1α (the ligand for CXC chemokine receptor 4 [CXCR4]) did not affect TGFP cell behavior. TCA-4 protein was not detected on the luminal surface of PLN HEVs in plt/plt mice, which have a congenital defect in T cell homing to PLNs. Accordingly, TGFP cells rolled but did not arrest in plt/plt HEVs. When TCA-4 was injected intracutaneously into plt/plt mice, the chemokine entered afferent lymph vessels and accumulated in draining PLNs. 2 h after intracutaneous injection, luminal presentation of TCA-4 was detectable in a subset of HEVs, and LFA-1–mediated TGFP cell adhesion was restored in these vessels. We conclude that TCA-4 is both required and sufficient for LFA-1 activation on rolling T cells in PLN HEVs. This study also highlights a hitherto undocumented role for chemokines contained in afferent lymph, which may modulate leukocyte recruitment in draining PLNs. PMID:10620605

  7. STUDIES ON TRANSMISSIBLE LYMPHOID LEUCEMIA OF MICE.

    PubMed

    Furth, J; Strumia, M

    1931-04-30

    Lymphoid leucemia of the mouse is readily transmitted by intravenous inoculations. The majority of the mice inoculated successfully develop leucemic, a smaller number of them, aleucemic lymphadenosis. The data presented favor the view that leucemic and aleucemic lymphadenosis are essentially the same condition. Leucemia produced by transmission is preceded by an aleucemic stage, in which the lymph nodes and the spleen are uniformly enlarged, and the white blood count and the percentage of lymphocytes are within the normal range but immature lymphocytes are numerous in the circulating blood. Young as well as old mice may develop leucemia if leucotic material enters their circulation. Studies of transmissible leucemia favor the view that leucemia of mammals is a neoplastic disease. The basic problem of leucemia would seem to be determination of the factors that bring about a malignant transformation of lymphoid cells.

  8. STUDIES ON TRANSMISSIBLE LYMPHOID LEUCEMIA OF MICE

    PubMed Central

    Furth, J.; Strumia, M.

    1931-01-01

    Lymphoid leucemia of the mouse is readily transmitted by intravenous inoculations. The majority of the mice inoculated successfully develop leucemic, a smaller number of them, aleucemic lymphadenosis. The data presented favor the view that leucemic and aleucemic lymphadenosis are essentially the same condition. Leucemia produced by transmission is preceded by an aleucemic stage, in which the lymph nodes and the spleen are uniformly enlarged, and the white blood count and the percentage of lymphocytes are within the normal range but immature lymphocytes are numerous in the circulating blood. Young as well as old mice may develop leucemia if leucotic material enters their circulation. Studies of transmissible leucemia favor the view that leucemia of mammals is a neoplastic disease. The basic problem of leucemia would seem to be determination of the factors that bring about a malignant transformation of lymphoid cells. PMID:19869876

  9. Innate lymphoid cells contribute to allergic airway disease exacerbation by obesity.

    PubMed

    Everaere, Laetitia; Ait-Yahia, Saliha; Molendi-Coste, Olivier; Vorng, Han; Quemener, Sandrine; LeVu, Pauline; Fleury, Sebastien; Bouchaert, Emmanuel; Fan, Ying; Duez, Catherine; de Nadai, Patricia; Staels, Bart; Dombrowicz, David; Tsicopoulos, Anne

    2016-11-01

    Epidemiologic and clinical observations identify obesity as an important risk factor for asthma exacerbation, but the underlying mechanisms remain poorly understood. Type 2 innate lymphoid cells (ILC2s) and type 3 innate lymphoid cells (ILC3s) have been implicated, respectively, in asthma and adipose tissue homeostasis and in obesity-associated airway hyperresponsiveness (AHR). We sought to determine the potential involvement of innate lymphoid cells (ILCs) in allergic airway disease exacerbation caused by high-fat diet (HFD)-induced obesity. Obesity was induced by means of HFD feeding, and allergic airway inflammation was subsequently induced by means of intranasal administration of house dust mite (HDM) extract. AHR, lung and visceral adipose tissue inflammation, humoral response, cytokines, and innate and adaptive lymphoid populations were analyzed in the presence or absence of ILCs. HFD feeding exacerbated allergic airway disease features, including humoral response, airway and tissue eosinophilia, AHR, and TH2 and TH17 pulmonary profiles. Notably, nonsensitized obese mice already exhibited increased lung ILC counts and tissue eosinophil infiltration compared with values in lean mice in the absence of AHR. The numbers of total and cytokine-expressing lung ILC2s and ILC3s further increased in HDM-challenged obese mice compared with those in HDM-challenged lean mice, and this was accompanied by high IL-33 and IL-1β levels and decreased ILC markers in visceral adipose tissue. Furthermore, depletion of ILCs with an anti-CD90 antibody, followed by T-cell reconstitution, led to a profound decrease in allergic airway inflammatory features in obese mice, including TH2 and TH17 infiltration. These results indicate that HFD-induced obesity might exacerbate allergic airway inflammation through mechanisms involving ILC2s and ILC3s. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  10. [Lymphoid infiltrates in the lung].

    PubMed

    Szalontai, K; Krenács, L; Csanádi, J; Ugocsai, K; Kraszkó, P

    1993-11-07

    The authors reviewed material of 10 year period (1980-1990) of the Department of Pulmonology, Albert Szent-Györgyi University of Medicine, Deszk, Hungary, and selected 14 patients from the files who considered to belong in one of the lymphoproliferative conditions (4 low grade and 4 high grade lymphomas of B-cell type, 1 angiocentric, 1 mediastinal lymphoblastic non-Hodgkin's lymphoma, 3 Hodgkin's lymphoma cases and 1 pleural pseudolymphoma). Every patient admitted with prominent pulmonary symptoms. The diagnoses were based on histology and immunohistochemistry of tissue samples and autopsy. One high grade B-cell and the angiocentric malignant lymphoma proved to be primary pulmonary process. No specific radiomorphological signs were found, which could be characteristic for the pulmonary lympho-reticular infiltrations and also to distinct the primary and secondary ones. The lung infiltrations in the most of the non-Hodgkin's lymphoma cases with low grade malignancy appeared imitating tuberculosis, while the high grade group and Hodgkin's lymphomas displayed confusion with any primary or multiple tumors.

  11. The Role of Lymphoid Neogenesis in Allografts.

    PubMed

    Hsiao, H-M; Li, W; Gelman, A E; Krupnick, A S; Kreisel, D

    2016-04-01

    De novo induction of organized lymphoid aggregates at nonlymphoid sites has been observed in many chronic inflammatory conditions where foreign antigens such as infectious agents, autoantigens or alloantigens, persist. The prevailing opinion in the field of transplantation is that lymphoid neogenesis within allografts is detrimental to the establishment of immune tolerance. These structures, commonly referred to as tertiary lymphoid organs (TLOs), are thought to contribute to graft rejection by generating and propagating local alloimmune responses. However, recent studies have shown that TLOs rich in regulatory Foxp3(+) cells are present in long-term accepting allografts. The notion that TLOs can contribute to the local downregulation of immune responses has been corroborated in other chronic inflammation models. These findings suggest that contrary to previous suggestions that the induction of TLOs in allografts is necessarily harmful, the induction of "tolerogenic" TLOs may prove advantageous. In this review, we discuss our current understanding of how TLOs are induced and how they regulate immune responses with a particular focus on alloimmunity.

  12. Earliest lymphoid colonization of neonatal rat lymph nodes: an antigen-specific process?

    PubMed

    Sainte-Marie, G

    2001-07-01

    The present work studied the little known process of lymphoid cell colonization of neonatal lymph nodes, while considering the nodal site of entry of circulating lymphoid cells and the either random or antigen-specific character of the process. Tissue sections of a mesenteric, cervical and popliteal node from each of 57 rats, aged 4 hours to 3 weeks, were analysed. Observations bear on the relative importance of the implication of the subcapsular sinus versus venules of nodes, and the composition of their emerging lymphoid cell population by determining the proportion of lymphocytes and blast-related cells. At 16-20 hours after birth, cell counts yielded a mean proportion of 84% for blast-related cells which decreased to 18% at 3 weeks. These percentages are compatible with values expected for a selective antigen-specific entry of lymphoid cells in nodes, not with values that would result from a random entry of lymphocytes. Moreover, observations revealed that by far most colonizing cells initially enter nodes carried by the afferent lymph, little via their venules.

  13. Morphology of the lymphoid organs of the bottlenose dolphin, Tursiops truncatus

    PubMed Central

    COWAN, DANIEL F.; SMITH, TOBY L.

    1999-01-01

    The anatomy of the lymphoid organs was studied during the course of detailed dissections of 50 beach-stranded bottlenose dolphins, Tursiops truncatus. Constant lymph nodes occur in 4 groups, based on their location and structure. These groups are somatic, including nodes of the cervical region and pelvic recess; lung-associated, included marginal, diaphragmatic and hilar nodes; visceral, including the mesenteric, pancreatic, pericolic and porta hepatis nodes; and aortic arch nodes. Lymphatic drainage of the lung is primarily to the marginal and diaphragmatic nodes. The mesenteric node mass is well-endowed with capsular and trabecular smooth muscle, and a network of muscle fascicles within the organ implies an important contractile function in the circulation of lymph. In addition to constant nodes, occasionally nodes are found in relation to the thoracic aorta, the kidney, and under the scapula. Gut-associated structures include dorsal and ventral oropharyngeal tonsils, mucosal aggregates in the straight segment of the intestine (colon) and anal tonsils; this gut-associated lymphoid tissue tends to involute with age, being greatly reduced by puberty. Formed lymphoid organs include the thymus and the spleen, the latter being relatively small in relation to body size. None of these structures is unique among cetaceans, but the anal tonsils are particularly well developed in T. truncatus. The lymphoid aggregates in the colon resemble the arrangement in the vermiform appendix, which is lacking in most cetaceans, and may have functions analogous to that organ. PMID:10445819

  14. Effect of selenium and vitamin E dietary deficiencies on chick lymphoid organ development (42361)

    SciTech Connect

    Marsh, J.A.; Combs, G.F. Jr.; Whitacre, M.E.; Dietert, R.R.

    1986-09-01

    Diets specifically deficient in selenium (Se) and/or vitamin E or adequate in both nutrients were fed to chicks from the time of hatching. Lymphoid organs (bursa, thymus, and in some instances, spleen) were collected from chicks 7-35 days of age. Growth of the chicks fed these diets was monitored over the experimental period as was lymphoid organ growth. The development of the primary lymphoid organs was further assessed by histological techniques and the organ contents of vitamin E (..cap alpha..-tocopherol) and Se were determined. Specific deficiencies of either Se or vitamin E were found to significantly impair bursal growth as did a combined deficiency. Thymic growth was impaired only by the combined deficiency diet. Severe histopathological changes in the bursa resulted from the combined deficiency and these were detectable by 10-14 days after hatching. These changes were characterized by a gradual degeneration of the epithelium and an accompanying depletion of lymphocytes. Similar changes, although slower to develop and less severe, were observed in the thymus as a result of the combined deficiency. When both serum and tissue levels of vitamin E and Se were monitored, it was observed that these were rapidly and independently depleted by the specific deficiency diets. These data suggest that the primary lymphoid organs are major targets of Se and vitamin E dietary deficiencies and provide a possible mechanism by which immune function may be impaired.

  15. Interleukin-27 inhibits ectopic lymphoid-like structure development in early inflammatory arthritis

    PubMed Central

    Bombardieri, Michele; Greenhill, Claire J.; McLeod, Louise; Nerviani, Alessandra; Rocher-Ros, Vidalba; Cardus, Anna; Williams, Anwen S.; Pitzalis, Costantino; Jenkins, Brendan J.

    2015-01-01

    Ectopic lymphoid-like structures (ELSs) reminiscent of secondary lymphoid organs often develop at sites of chronic inflammation where they contribute to immune-mediated pathology. Through evaluation of synovial tissues from rheumatoid arthritis (RA) patients, we now show that low interleukin-27 (IL-27) expression corresponds with an increased incidence of ELS and gene signatures associated with their development and activity. The presence of synovial ELS was also noted in mice deficient in the IL-27 receptor (IL-27R) after the onset of inflammatory arthritis. Here, pathology was associated with increased synovial expression of pro-inflammatory cytokines, homeostatic chemokines, and transcriptional regulators linked with lymphoid neogenesis. In both clinical and experimental RA, synovial ELS coincided with the heightened local expression of cytokines and transcription factors of the Th17 and T follicular helper (Tfh) cell lineages, and included podoplanin-expressing T cells within lymphoid aggregates. IL-27 inhibited the differentiation of podoplanin-expressing Th17 cells, and an increased number of these cells were observed in IL-27R–deficient mice with inflammatory arthritis. Thus, IL-27 appears to negatively regulate ELS development in RA through control of effector T cells. These studies open new opportunities for patient stratification and treatment. PMID:26417004

  16. Interleukin-27 inhibits ectopic lymphoid-like structure development in early inflammatory arthritis.

    PubMed

    Jones, Gareth W; Bombardieri, Michele; Greenhill, Claire J; McLeod, Louise; Nerviani, Alessandra; Rocher-Ros, Vidalba; Cardus, Anna; Williams, Anwen S; Pitzalis, Costantino; Jenkins, Brendan J; Jones, Simon A

    2015-10-19

    Ectopic lymphoid-like structures (ELSs) reminiscent of secondary lymphoid organs often develop at sites of chronic inflammation where they contribute to immune-mediated pathology. Through evaluation of synovial tissues from rheumatoid arthritis (RA) patients, we now show that low interleukin-27 (IL-27) expression corresponds with an increased incidence of ELS and gene signatures associated with their development and activity. The presence of synovial ELS was also noted in mice deficient in the IL-27 receptor (IL-27R) after the onset of inflammatory arthritis. Here, pathology was associated with increased synovial expression of pro-inflammatory cytokines, homeostatic chemokines, and transcriptional regulators linked with lymphoid neogenesis. In both clinical and experimental RA, synovial ELS coincided with the heightened local expression of cytokines and transcription factors of the Th17 and T follicular helper (Tfh) cell lineages, and included podoplanin-expressing T cells within lymphoid aggregates. IL-27 inhibited the differentiation of podoplanin-expressing Th17 cells, and an increased number of these cells were observed in IL-27R-deficient mice with inflammatory arthritis. Thus, IL-27 appears to negatively regulate ELS development in RA through control of effector T cells. These studies open new opportunities for patient stratification and treatment. © 2015 Jones et al.

  17. The origin and role of innate lymphoid cells in the lung.

    PubMed

    Lai, Deng-Ming; Shu, Qiang; Fan, Jie

    2016-01-01

    Innate lymphoid cells (ILCs), a newly identified member of the lymphoid population, play a critical role in the transition from innate to adaptive immunity in host defense. ILCs are important in mucosal barrier immunity, tissue homeostasis, and immune regulation throughout the body. Significant alterations in ILC responses in lung diseases have been observed and reported. Emerging evidence has shown that ILCs are importantly involved in the pathogenesis and development of a variety of lung diseases, i.e., helminth infections, allergic airway inflammation, and airway hyper-responsiveness. However, as a tissue-resident cell population, the role of ILCs in the lung remains poorly characterized. In this review, we discuss the role of ILCs in lung diseases, the mechanisms underlying the ILC-mediated regulation of immunity, and the therapeutic potential of modulating ILC responses.

  18. Characteristics of innate lymphoid cells (ILCs) and their role in immunological disorders (an update).

    PubMed

    Yazdani, Reza; Sharifi, Mehri; Shirvan, Aylar Saba; Azizi, Gholamreza; Ganjalikhani-Hakemi, Mazdak

    2015-01-01

    Innate lymphoid cells (ILCs) are a novel family of hematopoietic effectors and regulators of innate immunity. Although these cells are morphologically similar to B cells and T cells, however they do not express antigen receptors. ILCs seems to have emerging roles in innate immune responses against infectious or non-infectious microorganisms, protection of the epithelial barrier, lymphoid organogenesis and inflammation, tissue remodeling and regulating homeostasis of tissue stromal cells. In addition, it has recently been reported that ILCs have a crucial role in several disorders such as allergy and autoimmunity. Based on their phenotype and functions, ILCs are classified into three major groups called ILCs1, ILCs2, and ILCs3. Here we reviewed the most recent data concerning diverse ILC phenotypes, subclasses, functions in immune responses as well as in immune mediated disorders.

  19. Lymphoid cell kinetics under continuous low dose-rate gamma irradiation: A comparison study

    NASA Technical Reports Server (NTRS)

    Foster, B. R.

    1975-01-01

    A comparison study was conducted of the effects of continuous low dose-rate gamma irradiation on cell population kinetics of lymphoid tissue (white pulp) of the mouse spleen with findings as they relate to the mouse thymus. Experimental techniques employed included autoradiography and specific labeling with tritiated thymidine (TdR-(h-3)). The problem studied involved the mechanism of cell proliferation of lymphoid tissue of the mouse spleen and thymus under the stress of continuous irradiation at a dose rate of 10 roentgens (R) per day for 105 days (15 weeks). The aim was to determine whether or not a steady state or near-steady state of cell population could be established for this period of time, and what compensatory mechanisms of cell population were involved.

  20. Evidence of a true pharyngeal tonsil in birds: a novel lymphoid organ in Dromaius novaehollandiae and Struthio camelus (Palaeognathae)

    PubMed Central

    2012-01-01

    Background Tonsils are secondary lymphoid organs located in the naso- and oropharynx of most mammalian species. Most tonsils are characterised by crypts surrounded by dense lymphoid tissue. However, tonsils without crypts have also been recognised. Gut-associated lymphoid tissue (GALT), although not well-organised and lacking tonsillar crypts, is abundant in the avian oropharynx and has been referred to as the “pharyngeal tonsil”. In this context the pharyngeal folds present in the oropharynx of ratites have erroneously been named the pharyngeal tonsils. This study distinguishes between the different types and arrangements of lymphoid tissue in the pharyngeal region of D. novaehollandiae and S. camelus and demonstrates that both species possess a true pharyngeal tonsil which fits the classical definition of tonsils in mammals. Results The pharyngeal tonsil (Tonsilla pharyngea) of D. novaehollandiae was located on the dorsal free surface of the pharyngeal folds and covered by a small caudo-lateral extension of the folds whereas in S. camelus the tonsil was similarly located on the dorsal surface of the pharyngeal folds but was positioned retropharyngeally and encapsulated by loose connective tissue. The pharyngeal tonsil in both species was composed of lymph nodules, inter-nodular lymphoid tissue, mucus glands, crypts and intervening connective tissue septa. In S. camelus a shallow tonsillar sinus was present. Aggregated lymph nodules and inter-nodular lymphoid tissue was associated with the mucus glands on the ventral surface of the pharyngeal folds in both species and represented the Lymphonoduli pharyngeales. Similar lymphoid tissue, but more densely packed and situated directly below the epithelium, was present on the dorsal, free surface of the pharyngeal folds and represented a small, non-follicular tonsil. Conclusions The follicular pharyngeal tonsils in D. novaehollandiae and S. camelus are distinct from the pharyngeal folds in these species and

  1. Hallmarks of Tissue-Resident Lymphocytes

    PubMed Central

    Fan, Xiying; Rudensky, Alexander Y.

    2016-01-01

    Although they are classically viewed as continuously recirculating through the lymphoid organs and blood, lymphocytes also establish residency in non-lymphoid tissues, most prominently at barrier sites, including the mucosal surfaces and skin. These specialized tissue-resident lymphocyte subsets span the innate-adaptive continuum and include innate lymphoid cells (ILCs), unconventional T cells (e.g., NKT, MAIT, γδ T cells, and CD8αα+IELs), and tissue-resident memory T (TRM) cells. Although these diverse cell types differ in the particulars of their biology, they nonetheless exhibit important shared features, including a role in the preservation of tissue integrity and function during homeostasis, infection, and non-infectious perturbations. In this Review, we discuss the hallmarks of tissue-resident innate, innate-like, and adaptive lymphocytes, as well as their potential functions in non-lymphoid organs. PMID:26967286

  2. NK Cells and Other Innate Lymphoid Cells in Hematopoietic Stem Cell Transplantation.

    PubMed

    Vacca, Paola; Montaldo, Elisa; Croxatto, Daniele; Moretta, Francesca; Bertaina, Alice; Vitale, Chiara; Locatelli, Franco; Mingari, Maria Cristina; Moretta, Lorenzo

    2016-01-01

    Natural killer (NK) cells play a major role in the T-cell depleted haploidentical hematopoietic stem cell transplantation (haplo-HSCT) to cure high-risk leukemias. NK cells belong to the expanding family of innate lymphoid cells (ILCs). At variance with NK cells, the other ILC populations (ILC1/2/3) are non-cytolytic, while they secrete different patterns of cytokines. ILCs provide host defenses against viruses, bacteria, and parasites, drive lymphoid organogenesis, and contribute to tissue remodeling. In haplo-HSCT patients, the extensive T-cell depletion is required to prevent graft-versus-host disease (GvHD) but increases risks of developing a wide range of life-threatening infections. However, these patients may rely on innate defenses that are reconstituted more rapidly than the adaptive ones. In this context, ILCs may represent important players in the early phases following transplantation. They may contribute to tissue homeostasis/remodeling and lymphoid tissue reconstitution. While the reconstitution of NK cell repertoire and its role in haplo-HSCT have been largely investigated, little information is available on ILCs. Of note, CD34(+) cells isolated from different sources of HSC may differentiate in vitro toward various ILC subsets. Moreover, cytokines released from leukemia blasts (e.g., IL-1β) may alter the proportions of NK cells and ILC3, suggesting the possibility that leukemia may skew the ILC repertoire. Further studies are required to define the timing of ILC development and their potential protective role after HSCT.

  3. Type two innate lymphoid cells: the Janus cells in health and disease.

    PubMed

    Maazi, Hadi; Akbari, Omid

    2017-07-01

    Innate lymphoid cells are functionally diverse subsets of immune cells including the conventional natural killer cells, lymphoid tissue inducers, type 1, 2, and 3 with significant roles in immunity and pathogenesis of inflammatory diseases. Type 2 innate lymphoid cells (ILC2s) resemble type 2 helper (Th2) cells in cytokine production and contribute to anti-helminth immunity, maintaining mucosal tissue integrity, and adipose tissue browning. ILC2s play important roles in the pathogenesis of allergic diseases and asthma. Studying the pathways of activation and regulation of ILC2s are currently a priority for giving a better understanding of pathogenesis of diseases with immunological roots. Recently, our laboratory and others have shown several pathways of regulation of ILC2s by co-stimulatory molecules such as ICOS, regulatory T cells and by compounds such as nicotine. In this review, we summarize the current understanding of the mechanisms of activation and regulation of ILC2s and the role of these cells in health and disease. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Understanding Immune Cells in Tertiary Lymphoid Organ Development: It Is All Starting to Come Together.

    PubMed

    Jones, Gareth W; Hill, David G; Jones, Simon A

    2016-01-01

    Tertiary lymphoid organs (TLOs) are frequently observed in tissues affected by non-resolving inflammation as a result of infection, autoimmunity, cancer, and allograft rejection. These highly ordered structures resemble the cellular composition of lymphoid follicles typically associated with the spleen and lymph node compartments. Although TLOs within tissues show varying degrees of organization, they frequently display evidence of segregated T and B cell zones, follicular dendritic cell networks, a supporting stromal reticulum, and high endothelial venules. In this respect, they mimic the activities of germinal centers and contribute to the local control of adaptive immune responses. Studies in various disease settings have described how these structures contribute to either beneficial or deleterious outcomes. While the development and architectural organization of TLOs within inflamed tissues requires homeostatic chemokines, lymphoid and inflammatory cytokines, and adhesion molecules, our understanding of the cells responsible for triggering these events is still evolving. Over the past 10-15 years, novel immune cell subsets have been discovered that have more recently been implicated in the control of TLO development and function. In this review, we will discuss the contribution of these cell types and consider the potential to develop new therapeutic strategies that target TLOs.

  5. Retinoic acid differentially regulates the migration of innate lymphoid cell subsets to the gut

    PubMed Central

    Kim, Myung H.; Taparowsky, Elizabeth J.; Kim, Chang H.

    2015-01-01

    Summary Distinct groups of innate lymphoid cells (ILCs) such as ILC1, ILC2 and ILC3 populate the intestine, but how these ILCs develop tissue tropism for this organ is unclear. We report that prior to migration to the intestine ILCs first undergo a `switch' in their expression of homing receptors from lymphoid to gut homing receptors. This process is regulated by mucosal dendritic cells and the gut-specific tissue factor retinoic acid (RA). This change in homing receptors is required for long-term population and effector function of ILCs in the intestine. Only ILC1 and ILC3, but not ILC2, undergo the RA-dependent homing receptor switch in gut-associated lymphoid tissues. In contrast, ILC2 acquire gut homing receptors in a largely RA-independent manner during their development in the bone marrow and can migrate directly to the intestine. Thus, distinct programs regulate the migration of ILC subsets to the intestine for regulation of innate immunity. PMID:26141583

  6. Understanding Immune Cells in Tertiary Lymphoid Organ Development: It Is All Starting to Come Together

    PubMed Central

    Jones, Gareth W.; Hill, David G.; Jones, Simon A.

    2016-01-01

    Tertiary lymphoid organs (TLOs) are frequently observed in tissues affected by non-resolving inflammation as a result of infection, autoimmunity, cancer, and allograft rejection. These highly ordered structures resemble the cellular composition of lymphoid follicles typically associated with the spleen and lymph node compartments. Although TLOs within tissues show varying degrees of organization, they frequently display evidence of segregated T and B cell zones, follicular dendritic cell networks, a supporting stromal reticulum, and high endothelial venules. In this respect, they mimic the activities of germinal centers and contribute to the local control of adaptive immune responses. Studies in various disease settings have described how these structures contribute to either beneficial or deleterious outcomes. While the development and architectural organization of TLOs within inflamed tissues requires homeostatic chemokines, lymphoid and inflammatory cytokines, and adhesion molecules, our understanding of the cells responsible for triggering these events is still evolving. Over the past 10–15 years, novel immune cell subsets have been discovered that have more recently been implicated in the control of TLO development and function. In this review, we will discuss the contribution of these cell types and consider the potential to develop new therapeutic strategies that target TLOs. PMID:27752256

  7. Innate lymphoid cells in allergic and nonallergic inflammation.

    PubMed

    Morita, Hideaki; Moro, Kazuyo; Koyasu, Shigeo

    2016-11-01

    In the last decade, the full picture of the role of innate lymphoid cells (ILCs) has been gradually revealed. ILCs are classified into 3 groups based on their transcription factors and cytokine production patterns, which mirror helper T-cell subsets. Unlike T cells and B cells, ILCs do not have antigen receptors. They promptly respond to multiple tissue-derived factors, such as cytokines and alarmins, and produce multiple proinflammatory and immunoregulatory cytokines. It has been reported that ILC-derived cytokines are important for the induction and regulation of inflammation. Accumulating evidence suggests that ILCs play substantial roles in protection against infection and the pathogenesis of inflammatory diseases, such as allergic diseases and autoimmune diseases. Different ILC subsets localize in distinct tissue/organ niches and receive tissue-derived signals on different types of inflammation, which allows them to acquire diverse phenotypes with specialized effector capacities. In this review we highlight the roles of ILCs in a variety of organs, such as the airway, skin, and gastrointestinal tract, in the context of allergic and nonallergic inflammation. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  8. Expression of hpttg proto-oncogene in lymphoid neoplasias.

    PubMed

    Sáez, Carmen; Pereda, Teresa; Borrero, Juan J; Espina, Agueda; Romero, Francisco; Tortolero, María; Pintor-Toro, José A; Segura, Dolores I; Japón, Miguel A

    2002-11-21

    Pituitary tumor-transforming gene (pttg) is a distinct proto-oncogene which is expressed in certain normal tissues with high proliferation rate and in a variety of tumors. PTTG is the vertebrate analog of yeast securins Pds1 and Cut2 with a key role in the regulation of sister chromatid separation during mitosis. Impairment of PTTG regulated functions is expected to lead to chromosomal instability and aneuploidy. Human pttg (hpttg) is abundantly expressed in Jurkat T lymphoblastic lymphoma cells but not in normal peripheral blood leukocytes. To obtain additional data on the potential role of hpttg in lymphomagenesis we selected 150 cases of lymphoid tumors for the assessment of hpttg expression in tumor tissues. Immunohistochemical studies on formalin-fixed, paraffin-embedded tissues revealed hPTTG in 38.8% of B-cell lymphomas, 70.2% of T-cell lymphomas, and 73.1% of Hodgkin's lymphomas. Among B-cell lymphomas, the most frequently immunostained tumors were plasma cell tumors, diffuse large cell lymphomas, and follicle center cell lymphomas. In Hodgkin's disease, immunoreactivity was mainly noted in Reed-Sternberg cells. In conclusion, the frequent overexpression of hpttg in many histological subtypes of lymphoma suggests the involvement of this proto-oncogene in lymphomagenesis.

  9. Thymic lymphoid hyperplasia with multilocular thymic cysts diagnosed before the Sjögren syndrome diagnosis.

    PubMed

    Minato, Hiroshi; Kinoshita, Eriko; Nakada, Satoko; Nojima, Takayuki; Tanaka, Makoto; Usuda, Katsuo; Sagawa, Motoyasu; Iwao, Haruka; Tanaka, Masao; Doai, Mariko; Takahashi, Tomoko; Shibata, Naoko

    2015-07-16

    Thymic lymphoid hyperplasia is often present with myasthenia gravis as well as other autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis. Of the 4 cases of thymic lymphoid hyperplasia associated with Sjögren syndrome that have been reported, no case with a thymic lesion diagnosis that led to the diagnosis of Sjögren syndrome has been reported. We herein report a case of thymic lymphoid hyperplasia with multilocular thymic cysts, diagnosed before Sjögren syndrome. A 37-year-old Japanese woman had an approximate 5-cm anterior mediastinal mass detected by chest imaging. The resected lesion revealed multilocular thymic cysts that were filled with colloid-like material. Histology showed lymph follicular hyperplasia with many epithelial cysts. The epithelium consisted of thymic medullary epithelium, and no epithelial proliferation was seen in the lymphoid tissue. Lymphocytes were composed of an organized mixed population of mature T and B cells without significant atypia. The infiltrated B cells did not reveal light chain restriction or immunoglobulin heavy chain gene rearrangement. After the pathological diagnosis of thymic lesion, tests for the presence of autoantibodies were positive for antinuclear antibodies, rheumatic factor, and anti-SSA/Ro antibodies. The Schirmer's, chewing gum, and Saxon tests showed decreased salivary and lacrimal secretion. Lip biopsy showed focal lymphocytic sialadenitis. The signs and symptoms of Sjögren syndrome had not resolved, without aggravation, 1 year after the thymectomy. When a case with thymic lymphoid hyperplasia without myasthenia gravis is encountered, it is essential to consider the presence of another autoimmune disease including Sjögren syndrome.

  10. The Development of Adult Innate Lymphoid Cells

    PubMed Central

    Yang, Qi; Bhandoola, Avinash

    2016-01-01

    Innate lymphoid cells (ILC) are a specialized family of effector lymphocytes that transcriptionally and functionally mirror effector subsets of T cells, but differ from T cells in that they lack clonally-distributed adaptive antigen receptors. Our understanding of this family of lymphocytes is still in its infancy. In this review, we summarize current understanding and discuss recent insights into the cellular and molecular events that occur during early ILC development in adult mice. We discuss how these events overlap and diverge with the early development of adaptive T cells, and how they may influence the molecular and functional properties of mature ILC. PMID:26871595

  11. Effects of homozygosity of the nude (rnu) gene in an inbred strain of rats: studies of lymphoid and non--lymphoid organs in different age groups of nude rats of LEW background at a stage in the gene transfer.

    PubMed

    Hougen, H P; Klausen, B

    1984-01-01

    Several age groups of nude homozygous rnu/rnu and heterozygous rnu/+ rats of the same genetic background at an early stage of back-crossing (LEW/Mol) were compared as to body and organ weights, histological appearance and cell density of lymphoid organs, haematological values and differential counts of bone marrow and peripheral blood. No thymic tissue was found in the nude animals. 7-week-old nudes were smaller than control animals and had relatively larger non-lymphoid organs and cell-depleted peripheral lymphoid organs. Other age groups showed little difference. Peripheral blood of nude rats showed no signs of lymphopaenia in contrast with the findings in nude mice. The number of thoracic duct lymphocytes was, however, significantly smaller in all age groups of the nude rats, and the bone marrow tended to contain fewer lymphocytes.

  12. Diffuse nodular lymphoid hyperplasia of the small bowel associated with common variable immunodeficiency and giardiasis: a rare case report.

    PubMed

    Olmez, Sehmus; Aslan, Mehmet; Yavuz, Alpaslan; Bulut, Gulay; Dulger, Ahmet Cumhur

    2014-05-01

    Diffuse nodular lymphoid hyperplasia (DNLH) of the intestine is an extremely rare lymphoproliferative disorder of uncertain etiology. Typically, numerous polypoid nodules composed of hyperplastic benign lymphoid tissue are present in the small and/or large intestinal mucosa. DNLH has been observed in association with common variable immunodeficiency (CVID). A 38-years-old man was admitted to our clinic due to dyspeptic complaints. An upper gastrointestinal system endoscopic examination revealed DNLH in the duodenum. A biopsy specimen showed the presence of nodular lymphoid hyperplasia and a Giardia lamblia infection in the duodenum. CVID was suspected, and the diagnosis was established by demonstrating a significant reduction in the serum gamma-globulin levels. DNLH is a rare benign condition with regards to diagnosis and treatment of unknown etiology. In patients with DNLH, screening for the immune deficiencies is being important in addition to histopathological examinations.

  13. Retinoids Accelerate B Lineage Lymphoid Differentiation

    PubMed Central

    Chen, Xinrong; Esplin, Brandt L.; Garrett, Karla P.; Welner, Robert S.; Webb, Carol F.

    2008-01-01

    Retinoids are known to have potent effects on hematopoietic stem cell integrity, and our objective was to learn if they influence cells destined to replenish the immune system. Total CD19+ B lineage cells increased substantially in marrow and spleens of ATRA treated C57BL6 mice, while lymphoid progenitors were reduced. All B lymphoid progenitors were targets of ATRA in culture and overall cell yields declined without reductions in proliferation. Remarkably, ATRA shortened the time required for primitive progenitors to generate CD19+ cells. PCR analysis and a panel of RAR/RXR agonist treatments suggested that RARα mediates these responses. The transcription factors EBF1 and Pax-5 were elevated during treatment and ATRA had similar effects on human B cell differentiation. That is, it inhibited the expansion of human progenitor cells and accelerated their differentiation to B lineage cells. There may be previously unsuspected side effects of ATRA therapy, and the new findings suggest retinoids can normally contribute to the lymphopoietic environment in bone marrow. PMID:18097013

  14. Long-term Persistence of Innate Lymphoid Cells in the Gut After Intestinal Transplantation.

    PubMed

    Weiner, Joshua; Zuber, Julien; Shonts, Brittany; Yang, Suxiao; Fu, Jianing; Martinez, Mercedes; Farber, Donna L; Kato, Tomoaki; Sykes, Megan

    2017-10-01

    Little is known about innate lymphoid cell (ILC) populations in the human gut, and the turnover of these cells and their subsets after transplantation has not been described. Intestinal samples were taken from 4 isolated intestine and 3 multivisceral transplant recipients at the time of any operative resection, such as stoma closure or revision. ILCs were isolated and analyzed by flow cytometry. The target population was defined as being negative for lineage markers and double-positive for CD45/CD127. Cells were further stained to define ILC subsets and a donor-specific or recipient-specific HLA marker to analyze chimerism. Donor-derived ILCs were found to persist greater than 8 years after transplantation. Additionally, the percentage of cells thought to be lymphoid tissue inducer cells among donor ILCs was far higher than that among recipient ILCs. Our findings demonstrate that donor-derived ILCs persist long-term after transplantation and support the notion that human lymphoid tissue inducer cells may form in the fetus and persist throughout life, as hypothesized in rodents. Correlation between chimerism and rejection, graft failure, and patient survival requires further study.

  15. CollagenVI-Cre mice: A new tool to target stromal cells in secondary lymphoid organs

    PubMed Central

    Prados, Alejandro; Kollias, George; Koliaraki, Vasiliki

    2016-01-01

    Stromal cells in secondary lymphoid organs (SLOs) are non-hematopoietic cells involved in the regulation of adaptive immune responses. Three major stromal populations have been identified in adult SLOs: fibroblastic reticular cells (FRCs), follicular dendritic cells (FDCs) and marginal reticular cells (MRCs). The properties of these individual populations are not clearly defined, mainly due to the lack of appropriate genetic tools, especially for MRCs. Here, we analyzed stromal cell targeting in SLOs from a transgenic mouse strain that expresses Cre recombinase under the CollagenVI promoter, using lineage tracing approaches. We show that these mice target specifically MRCs and FDCs, but not FRCs in Peyer’s patches and isolated lymphoid follicles in the intestine. In contrast, stromal cells in lymph nodes and the spleen do not express the transgene, which renders ColVI-cre mice ideal for the specific targeting of stromal cells in the gut-associated lymphoid tissue (GALT). This funding further supports the hypothesis of organ-specific stromal precursors in SLOs. Interestingly, in all tissues analyzed, there was also high specificity for perivascular cells, which have been proposed to act as FDC precursors. Taken together, ColVI-Cre mice are a useful new tool for the dissection of MRC- and FDC-specific functions and plasticity in the GALT. PMID:27604178

  16. Gastric LTi cells promote lymphoid follicle formation but are limited by IRAK-M and do not alter microbial growth

    PubMed Central

    Shiu, Jessica; Piazuelo, M. Blanca; Ding, Hua; Czinn, Steven J.; Drakes, Maureen L.; Banerjee, Aditi; Basappa, Nisha; Kobayashi, Koichi S.; Fricke, W. Florian; Blanchard, Thomas G.

    2014-01-01

    Lymphoid tissue inducer (LTi) cells are activated by accessory cell IL-23, and promote lymphoid tissue genesis and antibacterial peptide production by the mucosal epithelium. We investigated the role of LTi cells in the gastric mucosa in the context of microbial infection. Mice deficient in IRAK-M, a negative regulator of TLR signaling, were investigated for increased LTi cell activity, and antibody mediated LTi cell depletion was used to analyze LTi cell dependent antimicrobial activity. H. pylori infected IRAK-M deficient mice developed increased gastric IL-17 and lymphoid follicles compared to wild type mice. LTi cells were present in naive and infected mice, with increased numbers in IRAK-M deficient mice by two weeks. Helicobacter and Candida infection of LTi cell depleted rag1−/− mice demonstrate