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Sample records for adoptively transferred immune

  1. Restoration of Viral Immunity in Immunodeficient Humans by the Adoptive Transfer of T Cell Clones

    NASA Astrophysics Data System (ADS)

    Riddell, Stanley R.; Watanabe, Kathe S.; Goodrich, James M.; Li, Cheng R.; Agha, Mounzer E.; Greenberg, Philip D.

    1992-07-01

    The adoptive transfer of antigen-specific T cells to establish immunity is an effective therapy for viral infections and tumors in animal models. The application of this approach to human disease would require the isolation and in vitro expansion of human antigen-specific T cells and evidence that such T cells persist and function in vivo after transfer. Cytomegalovirus-specific CD8^+ cytotoxic T cell (CTL) clones could be isolated from bone marrow donors, propagated in vitro, and adoptively transferred to immunodeficient bone marrow transplant recipients. No toxicity developed and the clones provided persistent reconstitution of CD8^+ cytomegalovirus-specific CTL responses.

  2. [Adoptive transfer of immunity against Nippostrongylus brasiliensis in mice. In vitro restimulation of immune cells before their transfer].

    PubMed

    Rhalem, A; Bourdieu, C; Luffau, G; Péry, P

    1989-01-01

    When mesenteric lymph node cells from infected mice were stimulated during an in vitro culture with exoantigens or with a purified protective antigen of Nippostrongylus brasiliensis, a drop was noted in the number of cells required to transfer protection to new mice. A maximal effect was already obtained after 4 hrs. of culture, but irradiated cells or cells from another mouse strain were unable to mediate this transfer. T cells were more effective than B cells in transferring the protection.

  3. Extending the lifespan and efficacies of immune cells used in adoptive transfer for cancer immunotherapies–A review

    PubMed Central

    Nayar, Sandeep; Dasgupta, Prokar; Galustian, Christine

    2015-01-01

    Cells used in adoptive cell-transfer immunotherapies against cancer include dendritic cells (DCs), natural-killer cells, and CD8+ T-cells. These cells may have limited efficacy due to their lifespan, activity, and immunosuppressive effects of tumor cells. Therefore, increasing longevity and activity of these cells may boost their efficacy. Four cytokines that can extend immune effector-cell longevity are IL-2, IL-7, IL-21, and IL-15. This review will discuss current knowledge on effector-cell lifespans and the mechanisms by which IL-2, IL-7, IL-15, and IL-21 can extend effector-cell longevity. We will also discuss how lifespan and efficacy of these cells can be regulated to allow optimal clinical benefits. PMID:26155387

  4. Vaccination of Lewis rats with temperature-sensitive mutants of Mycoplasma pulmonis: adoptive transfer of immunity by spleen cells but not by sera.

    PubMed Central

    Lai, W C; Bennett, M; Lu, Y S; Pakes, S P

    1991-01-01

    Temperature-sensitive mutant vaccines protect rats against Mycoplasma pulmonis infection. The role of the humoral or cellular immune response in resistance to mycoplasma infection was investigated by adoptive-transfer experiments. Spleen cells from Lewis rats vaccinated but not challenged with wild-type organisms (vaccinated) and spleen cells from rats vaccinated (or not) and challenged were effective in preventing syngeneic recipients from developing respiratory disease. There was also a significant reduction in the incidence and number of challenging organisms in the respiratory system. In contrast, sera from the same donors had no detectable effect on the number of mycoplasmas recovered or on lesion development in the respiratory tract. We conclude that cellular immunity rather than humoral immunity generated in vaccinated rats confers protection against subsequent infection. PMID:1987049

  5. Cutaneous sensitivity induced by immunization with irradiated Schistosoma mansoni cercariae. I. Induction, elicitation, and adoptive transfer analysis of cell-mediated cutaneous sensitivity

    SciTech Connect

    Ch'ang, L.Y.; Colley, D.G.

    1986-06-01

    Exposure of C57BL/6 mice to highly irradiated (50 kR) cercariae of Schistosoma mansoni leads to the development of partial resistance against subsequent challenge with unattenuated cercariae. We have analyzed the cellular immune responses that occur during the afferent and efferent phases of this protective sensitization. Mice were immunized by exposure to irradiated S. mansoni cercariae. After challenge with irradiated cercariae, delayed-type (18-72 hr) cutaneous sensitivity reaction sites were rich in mononuclear cells and eosinophils. This reactivity was established by 4 days after sensitization, reached its maximum between 7 and 14 days after sensitization, and was maintained for over 20 weeks. These challenge reactions could be abrogated by treatment with either 200 mg/kg cyclophosphamide or 5 mg of hydrocortisone. Syngeneic adoptive transfer of cutaneous sensitivity was accomplished with lymphoid cells from the draining lymph nodes or spleens of mice sensitized 7-14 days previously. Negative selection studies of nylon-wool non-adherent cells from sensitized donors demonstrated that the cells responsible for transferring this eosinophil-rich, delayed-type cutaneous sensitivity to S. mansoni irradiated cercariae were Thy/sup -1 +/, Lyt/sup 1 +/, Lyt/sup 2 -/, surface Ig/sup -/ lymphocytes.

  6. Maternal immune transfer in mollusc.

    PubMed

    Wang, Lingling; Yue, Feng; Song, Xiaorui; Song, Linsheng

    2015-02-01

    Maternal immunity refers to the immunity transferred from mother to offspring via egg, playing an important role in protecting the offspring at early life stages and contributing a trans-generational effect on offspring's phenotype. Because fertilization is external in most of the molluscs, oocytes and early embryos are directly exposed to pathogens in the seawater, and thus maternal immunity could provide a better protection before full maturation of their immunological systems. Several innate immune factors including pattern recognition receptors (PRRs) like lectins, and immune effectors like lysozyme, lipopolysaccharide binding protein/bacterial permeability-increasing proteins (LBP/BPI) and antioxidant enzymes have been identified as maternally derived immune factors in mollusc eggs. Among these immune factors, some maternally derived lectins and antibacterial factors have been proved to endue mollusc eggs with effective defense ability against pathogen infection, while the roles of other factors still remain untested. The physiological condition of mollusc broodstock has a profound effect on their offspring fitness. Many other factors such as nutrients, pathogens, environment conditions and pollutants could exert considerable influence on the maternal transfer of immunity. The parent molluscs which have encountered an immune stimulation endow their offspring with a trans-generational immune capability to protect them against infections effectively. The knowledge on maternal transfer of immunity and the trans-generational immune effect could provide us with an ideal management strategy of mollusc broodstock to improve the immunity of offspring and to establish a disease-resistant family for a long-term improvement of cultured stocks.

  7. Mechanisms of immunological eradication of a syngeneic guinea pig tumor. II. Effect of methotrexate treatment and T cell depletion of the recipient on adoptive immunity

    SciTech Connect

    Shu, S.; Fonseca, L.S.; Hunter, J.T.; Rapp, H.J.

    1983-01-01

    The influence of methotrexate on the development of immunity to the line 10 hepatoma was studied in guinea pigs. Chronic methotrexate treatment had no apparent effect on the ability of immune guinea pigs to suppress the growth of inoculated tumor cells. In contrast, the same methotrexate regimen inhibited the development of tumor immunity if started before the 8th day after immunization with a vaccine containing viable line 10 cells admixed with Bacillus Calmette-Guerin (BCG) cell walls. Thus, methotrexate selectively inhibited the afferent limb of the immune response. In adoptive transfer experiments, methotrexate-treated recipient guinea pigs were capable of being passively sensitized with immune spleen cells, indicating that the primary cell-mediated immune response of the recipient was not required for adoptive immunity. The contribution of recipient T cells in adoptive immunity was further investigated in guinea pigs deleted of T cells by thymectomy, irradiation, and bone marrow reconstitution. Despite demonstrable deficiency in T lymphocyte reactions, B animals were fully capable of rejecting tumors after transfer of immune cells. These results suggest that the expression of adoptive immunity was independent of recipient T cell participation. In addition, sublethal irradiation of immune spleen cells prior to adoptive transfer abolished their efficacy. Proliferation of transferred immune cells in the recipient may be essential for expression of adoptive immunity.

  8. ADOPTIVE-CELL-TRANSFER THERAPY FOR THE TREATMENT OF PATIENTS WITH CANCER

    PubMed Central

    Dudley, Mark E.; Rosenberg, Steven A.

    2008-01-01

    Adoptive immunotherapy — the isolation of antigen-specific cells, their ex vivo expansion and activation, and subsequent autologous administration — is a promising approach to inducing antitumour immune responses. The molecular identification of tumour antigens and the ability to monitor the persistence and transport of transferred cells has provided new insights into the mechanisms of tumour immunotherapy. Recent studies have shown the effectiveness of cell-transfer therapies for the treatment of patients with selected metastatic cancers. These studies provide a blueprint for the wider application of adoptive-cell-transfer therapy, and emphasize the requirement for in vivo persistence of the cells for therapeutic efficacy. PMID:12951585

  9. Trial Watch: Adoptive cell transfer for oncological indications

    PubMed Central

    Aranda, Fernando; Buqué, Aitziber; Bloy, Norma; Castoldi, Francesca; Eggermont, Alexander; Cremer, Isabelle; Fridman, Wolf Hervé; Fucikova, Jitka; Galon, Jérôme; Spisek, Radek; Tartour, Eric; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

    2015-01-01

    One particular paradigm of anticancer immunotherapy relies on the administration of (potentially) tumor-reactive immune effector cells. Generally, these cells are obtained from autologous peripheral blood lymphocytes (PBLs) ex vivo (in the context of appropriate expansion, activation and targeting protocols), and re-infused into lymphodepleted patients along with immunostimulatory agents. In spite of the consistent progress achieved throughout the past two decades in this field, no adoptive cell transfer (ACT)-based immunotherapeutic regimen is currently approved by regulatory agencies for use in cancer patients. Nonetheless, the interest of oncologists in ACT-based immunotherapy continues to increase. Accumulating clinical evidence indicates indeed that specific paradigms of ACT, such as the infusion of chimeric antigen receptor (CAR)-expressing autologous T cells, are associated with elevated rates of durable responses in patients affected by various neoplasms. In line with this notion, clinical trials investigating the safety and therapeutic activity of ACT in cancer patients are being initiated at an ever increasing pace. Here, we review recent preclinical and clinical advances in the development of ACT-based immunotherapy for oncological indications. PMID:26451319

  10. Immune Checkpoint Blockade to Improve Tumor Infiltrating Lymphocytes for Adoptive Cell Therapy

    PubMed Central

    Kodumudi, Krithika N.; Siegel, Jessica; Weber, Amy M.; Scott, Ellen; Sarnaik, Amod A.; Pilon-Thomas, Shari

    2016-01-01

    Tumor-infiltrating lymphocytes (TIL) has been associated with improved survival in cancer patients. Within the tumor microenvironment, regulatory cells and expression of co-inhibitory immune checkpoint molecules can lead to the inactivation of TIL. Hence, there is a need to develop strategies that disrupt these negative regulators to achieve robust anti-tumor immune responses. We evaluated the blockade of immune checkpoints and their effect on T cell infiltration and function. We examined the ability of TIL to induce tumor-specific immune responses in vitro and in vivo. TIL isolated from tumor bearing mice were tumor-specific and expressed co-inhibitory immune checkpoint molecules. Administration of monoclonal antibodies against immune checkpoints led to a significant delay in tumor growth. However, anti-PD-L1 antibody treated mice had a significant increase in T cell infiltration and IFN-γ production compared to other groups. Adoptive transfer of in vitro expanded TIL from tumors of anti-PD-L1 antibody treated mice led to a significant delay in tumor growth. Blockade of co-inhibitory immune checkpoints could be an effective strategy to improve TIL infiltration and function. PMID:27050669

  11. Engineering antitumor immunity by T-cell adoptive immunotherapy.

    PubMed

    Riddell, Stanley R

    2007-01-01

    The adoptive transfer of antigen-specific T cells has been used successfully to treat experimental tumors in animal models and viral infections in humans, but harnessing the exquisite specificity and potency of T cells to treat human malignancy has proven challenging. The efforts to use T cells to treat patients with cancer have often been informative in identifying limitations that must be overcome to improve therapeutic efficacy, and a clearer picture of the requirements for successful adoptive T-cell transfer is gradually emerging. Indolent and a subset of aggressive B-cell lymphomas in humans have been shown to be susceptible to eradication by T cells in clinical settings where highly immunogenic minor histocompatibility or viral antigens are presented by tumor cells. In this article, we will review how recent advances in our understanding of the properties of antigen-specific T cells that facilitate their long-term persistence in vivo and reversion to the memory pool after in vitro culture, combined with approaches to molecularly engineer T cells with receptors that target molecules expressed by B-cell lymphoma, are providing opportunities to broaden the application of T-cell therapy and improve its efficacy for this disease.

  12. Information Transfer and the Adoption of Agricultural Innovations.

    ERIC Educational Resources Information Center

    Longo, Rose Mary Juliano

    1990-01-01

    Data collected in the Federal District of Brazil were analyzed in terms of information transfer through mass media and interpersonal communication and how they influence farmers in the Federal District of Brazil in their decisions to adopt agricultural innovations. (42 references) (EAM)

  13. Serologic testing to verify the immune status of internationally adopted children against vaccine preventable diseases☆

    PubMed Central

    Staat, Mary Allen; Stadler, Laura Patricia; Donauer, Stephanie; Trehan, Indi; Rice, Marilyn; Salisbury, Shelia

    2010-01-01

    Definitive immunization guidelines for internationally adopted children are lacking. We examined whether these children had serologic evidence of protection against vaccine-preventable diseases. For children with ≥3 vaccine doses, overall protection was high for diphtheria (85%), tetanus (95%), polio (93%), hepatitis B (77%), and Hib (67%). For children ≥12 months of age with ≥1 dose of measles, mumps, or rubella vaccines, 95%, 72%, and 94% were immune, respectively. Children without immunization documentation had lower immunity. Serologic testing was useful in verifying the immunization status in internationally adopted children with and without documentation of immunizations. PMID:20937322

  14. Improvement of adoptive cellular immunotherapy of human cancer using ex-vivo gene transfer.

    PubMed

    Paul, Stephane; Calmels, Bastien; Acres, R Bruce

    2002-02-01

    A variety of adoptive cellular strategies, aimed at boosting the immune system, have been tested in the management of metastatic diseases. Despite the drawbacks associated with ex vivo cell manipulation and upscaling, several such approaches have been assessed in the clinic. The use of lymphokine-activated killer (LAK) cells, auto-lymphocyte therapy (ALT) and tumor-infiltrating lymphocytes (TIL) have been the best studied and further trials are ongoing. Thus far, these approaches have not consistently shown benefit when compared to standard immune-based treatment with biologic response modifiers, notably, high-dose interleukin-2 (IL-2). More recently, it has been shown, in various animal models, that the ex vivo transfer of genes to cells of the immune system can have a dramatic impact on cancer immunotherapy. The application of gene transfer techniques to immunotherapy has animated the field of cell-based cancer therapy research. A wide variety of viral and non-viral gene transfer methods have been investigated in this context. Ex vivo strategies include gene delivery into tumor cells and into cellular components of the immune system, including cytotoxic T cells, NK, macrophages and dendritic cells (DC). Several of these approaches have already been translated into cancer therapy clinical trials. In this review, we focus on the rationale and types of ex vivo gene-based immunotherapy of cancer. Finally, the use of genetically modified DC for tumor vaccination and its prospects are discussed. PMID:12108977

  15. Targeting STAT3 in adoptively transferred T cells promotes their in vivo expansion and antitumor effects

    PubMed Central

    Kujawski, Maciej; Zhang, Chunyan; Herrmann, Andreas; Reckamp, Karen; Scuto, Anna; Jensen, Michael; Deng, Jiehui; Forman, Stephen; Figlin, Robert; Yu, Hua

    2010-01-01

    Adoptive cell therapy with engineered T cells to improve natural immune response and antitumor functions has shown promise for treating cancer. However, the requirement for extensive ex vivo manipulation of T cells and the immunosuppressive effects of the tumor microenvironment limit this therapeutic modality. In the present study, we investigated the possibility to circumvent these limitations by engineering Stat3-deficient CD8+ T cells or by targeting Stat3 in the tumor microenvironment. We show that ablating Stat3 in CD8+ T cells prior to their transfer allows their efficient tumor infiltration and robust proliferation, resulting in increased tumor antigen-specific T cell activity and tumor growth inhibition. For potential clinical translation, we combined adoptive T cell therapy with an FDA-approved tyrosine kinase inhibitor, sunitinib, in renal cell carcinoma and melanoma tumor models. Sunitinib inhibited Stat3 in dendritic cells and T cells, reduced conversion of transferred Foxp3− T cells to tumor-associated T regulatory cells while increasing transferred CD8+ T cell infiltration and activation at the tumor site, leading to inhibition of primary tumor growth. These data demonstrate that adoptively transferred T cells can be expanded and activated in vivo either by engineering Stat3 silenced T cells or by targeting Stat3 systemically with small-molecule inhibitors. PMID:21118964

  16. Multifunctional T-cell Analyses to Study Response and Progression in Adoptive Cell Transfer Immunotherapy

    PubMed Central

    Ma, Chao; Cheung, Ann F.; Chodon, Thinle; Koya, Richard C.; Wu, Zhongqi; Ng, Charles; Avramis, Earl; Cochran, Alistair J.; Witte, Owen N.; Baltimore, David; Chmielowski, Bartosz; Economou, James S.; Comin-Anduix, Begonya; Ribas, Antoni; Heath, James R.

    2013-01-01

    Adoptive cell transfer (ACT) of genetically engineered T cells expressing cancer-specific T-cell receptors (TCR) is a promising cancer treatment. Here, we investigate the in vivo functional activity and dynamics of the transferred cells by analyzing samples from 3 representative patients with melanoma enrolled in a clinical trial of ACT with TCR transgenic T cells targeted against the melanosomal antigen MART-1. The analyses included evaluating 19 secreted proteins from individual cells from phenotypically defined T-cell subpopulations, as well as the enumeration of T cells with TCR antigen specificity for 36 melanoma antigens. These analyses revealed the coordinated functional dynamics of the adoptively transferred, as well as endogenous, T cells, and the importance of highly functional T cells in dominating the antitumor immune response. This study highlights the need to develop approaches to maintaining antitumor T-cell functionality with the aim of increasing the long-term efficacy of TCR-engineered ACT immunotherapy. SIGNIFICANCE A longitudinal functional study of adoptively transferred TCR–engineered lymphocytes yielded revealing snapshots for understanding the changes of antitumor responses over time in ACT immunotherapy of patients with advanced melanoma. PMID:23519018

  17. Stable activity of diabetogenic cells with age in NOD mice: dynamics of reconstitution and adoptive diabetes transfer in immunocompromised mice

    PubMed Central

    Kaminitz, Ayelet; Mizrahi, Keren; Ash, Shifra; Ben-Nun, Avi; Askenasy, Nadir

    2014-01-01

    The non-obese diabetic (NOD) mouse is a prevalent disease model of type 1 diabetes. Immune aberrations that cause and propagate autoimmune insulitis in these mice are being continually debated, with evidence supporting both dominance of effector cells and insufficiency of suppressor mechanisms. In this study we assessed the behaviour of NOD lymphocytes under extreme expansion conditions using adoptive transfer into immunocompromised NOD.SCID (severe combined immunodeficiency) mice. CD4+ CD25+ T cells do not cause islet inflammation, whereas splenocytes and CD4+ CD25− T cells induce pancreatic inflammation and hyperglycaemia in 80–100% of the NOD.SCID recipients. Adoptively transferred effector T cells migrate to the lymphoid organs and pancreas, proliferate, are activated in the target organ in situ and initiate inflammatory insulitis. Reconstitution of all components of the CD4+ subset emphasizes the plastic capacity of different cell types to adopt effector and suppressor phenotypes. Furthermore, similar immune profiles of diabetic and euglycaemic NOD.SCID recipients demonstrate dissociation between fractional expression of CD25 and FoxP3 and the severity of insulitis. There were no evident and consistent differences in diabetogenic activity and immune reconstituting activity of T cells from pre-diabetic (11 weeks) and new onset diabetic NOD females. Similarities in immune phenotypes and variable distribution of effector and suppressor subsets in various stages of inflammation commend caution in interpretation of quantitative and qualitative aberrations as markers of disease severity in adoptive transfer experiments. PMID:24601987

  18. Stable activity of diabetogenic cells with age in NOD mice: dynamics of reconstitution and adoptive diabetes transfer in immunocompromised mice.

    PubMed

    Kaminitz, Ayelet; Mizrahi, Keren; Ash, Shifra; Ben-Nun, Avi; Askenasy, Nadir

    2014-07-01

    The non-obese diabetic (NOD) mouse is a prevalent disease model of type 1 diabetes. Immune aberrations that cause and propagate autoimmune insulitis in these mice are being continually debated, with evidence supporting both dominance of effector cells and insufficiency of suppressor mechanisms. In this study we assessed the behaviour of NOD lymphocytes under extreme expansion conditions using adoptive transfer into immunocompromised NOD.SCID (severe combined immunodeficiency) mice. CD4(+)  CD25(+) T cells do not cause islet inflammation, whereas splenocytes and CD4(+)  CD25(-) T cells induce pancreatic inflammation and hyperglycaemia in 80-100% of the NOD.SCID recipients. Adoptively transferred effector T cells migrate to the lymphoid organs and pancreas, proliferate, are activated in the target organ in situ and initiate inflammatory insulitis. Reconstitution of all components of the CD4(+) subset emphasizes the plastic capacity of different cell types to adopt effector and suppressor phenotypes. Furthermore, similar immune profiles of diabetic and euglycaemic NOD.SCID recipients demonstrate dissociation between fractional expression of CD25 and FoxP3 and the severity of insulitis. There were no evident and consistent differences in diabetogenic activity and immune reconstituting activity of T cells from pre-diabetic (11 weeks) and new onset diabetic NOD females. Similarities in immune phenotypes and variable distribution of effector and suppressor subsets in various stages of inflammation commend caution in interpretation of quantitative and qualitative aberrations as markers of disease severity in adoptive transfer experiments.

  19. A New Hope in Immunotherapy for Malignant Gliomas: Adoptive T Cell Transfer Therapy

    PubMed Central

    Chung, Dong-Sup; Shin, Hye-Jin; Hong, Yong-Kil

    2014-01-01

    Immunotherapy emerged as a promising therapeutic approach to highly incurable malignant gliomas due to tumor-specific cytotoxicity, minimal side effect, and a durable antitumor effect by memory T cells. But, antitumor activities of endogenously activated T cells induced by immunotherapy such as vaccination are not sufficient to control tumors because tumor-specific antigens may be self-antigens and tumors have immune evasion mechanisms to avoid immune surveillance system of host. Although recent clinical results from vaccine strategy for malignant gliomas are encouraging, these trials have some limitations, particularly their failure to expand tumor antigen-specific T cells reproducibly and effectively. An alternative strategy to overcome these limitations is adoptive T cell transfer therapy, in which tumor-specific T cells are expanded ex vivo rapidly and then transferred to patients. Moreover, enhanced biologic functions of T cells generated by genetic engineering and modified immunosuppressive microenvironment of host by homeostatic T cell expansion and/or elimination of immunosuppressive cells and molecules can induce more potent antitumor T cell responses and make this strategy hold promise in promoting a patient response for malignant glioma treatment. Here we will review the past and current progresses and discuss a new hope in adoptive T cell therapy for malignant gliomas. PMID:25009822

  20. Adoption

    MedlinePlus

    ... the birth nor adoptive parents know the others' identities. Other adoptions are handled more openly. Open adoptions, ... desire to seek out more information about the identity of the birth family. Most of us (whether ...

  1. Treatment of dextran sodium sulfate-induced experimental colitis by adoptive transfer of peritoneal cells

    PubMed Central

    Liu, Ting; Ren, Jun; Wang, Wei; Wei, Xia-wei; Shen, Guo-bo; Liu, Yan-tong; Luo, Min; Xu, Guang-chao; Shao, Bin; Deng, Sen-yi; He, Zhi-yao; Liang, Xiao; Liu, Yu; Wen, Yan-Zhu; Xiang, Rong; Yang, Li; Deng, Hong-xin; Wei, Yu-quan

    2015-01-01

    The adoptive transfer of the natural regulatory B cells and macrophages should be a useful treatment for inflammation and autoimmune disease. However, it is usually difficult to isolate these cells from the tissues and expand them. Here, we investigated the feasibility of adoptively transferring peritoneal cells (PCs) as a treatment for DSS-induced colitis. We found that peritoneal cavity can provide an easily accessible site for harvesting enough number of PCs, namely, two-dose PCs for the treatment from a mouse in one operation. Adoptive therapy of these cells from healthy mice or those with disease is effectively in reducing the disease activity score. The natural B cells and macrophages of the infused PCs can selectively migrate to lesion sites and regulate the expression of Stat3, NF−κB, Smad3 and Smad7. Additionally, PCs exert dual activity of IL-10 and TGF-β secreted spontaneously by both peritoneal B cells and macrophages, which in turn enhance the induction of regulatory B cells and Macrophages in microenvironment of inflammation. Moreover, PCs can re-establish immunological tolerance in the OVA-immunized mice. Thus, our findings provide a new strategy for colitis therapy and could be of importance in additional exploration of other inflammation and autoimmune diseases therapy. PMID:26565726

  2. The cellular transfer of immunity to Nippostrongylus brasiliensis in inbred rats (Lewis strain)

    PubMed Central

    Kelly, J. D.; Dineen, J. K.

    1972-01-01

    Mesenteric lymph node cells obtained from highly inbred donor rats (Lewis strain), resistant to Nippostrongylus brasiliensis infection, were syngeneically transferred by intravenous injection into previously uninfected recipients. The adoptively immunized recipients were then challenged with either 1500 or 3000 third stage N. brasiliensis larvae on the day of cell transfer. The degree of resistance transferred was assessed by monitoring daily faecal egg output, differential worm burdens on days 6 and 10 of infection and the number of eggs per uterus in gravid worms. The syngeneic transfer of 100 × 106 immune mesenteric lymph node cells invariably resulted in suppression of egg production, a two- to four-fold reduction in the number of eggs per uterus in gravid females and rejection of at least 75 per cent of adult worms by days 6 and 10 of infection. It was also noted that mesenteric lymph node cells obtained from donors on day 15 of a primary infection were more effective than those obtained from donors immunized by multiple infections. Immune cells transferred from donors on day 4 of infection were equally effective with those transferred on day 0. However, immune cells transferred on or after day 10 of infection had little or no effect and this shows that the parasite is less susceptible to an attack mounted by the transferred cells during the later stages of infection. PMID:5062015

  3. Protection against rat vaginal candidiasis by adoptive transfer of vaginal B lymphocytes.

    PubMed

    De Bernardis, Flavia; Santoni, Giorgio; Boccanera, Maria; Lucciarini, Roberta; Arancia, Silvia; Sandini, Silvia; Amantini, Consuelo; Cassone, Antonio

    2010-06-01

    Vulvovaginal candidiasis is a mucosal infection affecting many women, but the immune mechanisms operating against Candida albicans at the mucosal level remain unknown. A rat model was employed to further characterize the contribution of B and T cells to anti-Candida vaginal protection. Particularly, the protective role of vaginal B cells was studied by means of adoptive transfer of vaginal CD3(-) CD5(+) IgM(+) cells from Candida-immunized rats to naïve animals. This passive transfer of B cells resulted into a number of vaginal C. albicans CFU approximately 50% lower than their controls. Sorted CD3(-) CD5(+) IgM(+) vaginal B lymphocytes from Candida-infected rats proliferated in response to stimulation with an immunodominant mannoprotein (MP) antigen of the fungus. Importantly, anti-MP antibodies and antibody-secreting B cells were detected in the supernatant and cell cultures, respectively, of vaginal B lymphocytes from infected rats incubated in vitro with vaginal T cells and stimulated with MP. No such specific antibodies were found when using vaginal B cells from uninfected rats. Furthermore, inflammatory and anti-inflammatory cytokines, such as interleukin-2 (IL-2), IL-6 and IL-10, were found in the supernatant of vaginal B cells from infected rats. These data are evidence of a partial anti-Candida protective role of CD3(-) CD5(+) IgM(+) vaginal B lymphocytes in our experimental model.

  4. Adoptive transfer of macrophages from adult mice reduces mortality in mice infected with human enterovirus 71.

    PubMed

    Liu, Jiangning; Li, Xiaoying; Fan, Xiaoxu; Ma, Chunmei; Qin, Chuan; Zhang, Lianfeng

    2013-02-01

    Human enterovirus 71 (EV71) causes hand, foot and mouth disease in children under 6 years of age, and the neurological complications of this virus can lead to death. Until now, no vaccines or drugs have been available for the clinical control of this epidemic. Macrophages can engulf pathogens and mediate a series of host immune responses that play a role in the defence against infectious diseases. Using immunohistochemistry, we observed the localizations of virus in muscle tissues of EV71-infected mice. The macrophages isolated from the adult mice could kill the virus gradually in vitro, as shown using quantitative real-time PCR (qRT-PCR) and virus titration. Co-localisation of lysosomes and virus within macrophages suggested that the lysosomes were possibly responsible for the phagocytosis of EV71. Activation of the macrophages in the peritoneal cavity of mice four days pre-infection reduced the mortality of mice upon lethal EV71 infection. The adoptive transfer of macrophages from adult mice inhibited virus replication in the muscle tissues of infected mice, and this was followed by a relief of symptoms and a significant reduction of mortality, which suggested that the adoptive transfer of macrophages from adult humans represents a potential strategy to treat EV71-infected patients.

  5. Characterization of the natural killer T-cell response in an adoptive transfer model of atherosclerosis.

    PubMed

    VanderLaan, Paul A; Reardon, Catherine A; Sagiv, Yuval; Blachowicz, Lydia; Lukens, John; Nissenbaum, Michael; Wang, Chyung-Ru; Getz, Godfrey S

    2007-03-01

    Natural killer T (NKT) cells have recently been implicated in atherogenesis, primarily for their ability to recognize and respond to lipid antigens. Because the atherosclerotic lesion is characterized by the retention and modification of lipids in the vascular wall, NKT cells may be involved in promoting the local vascular inflammatory response. Here, we investigate the proatherogenic role of NKT cells in an adoptive transfer model of atherosclerosis, using as recipients immune-deficient, atherosclerosis-susceptible RAG1(-/-)LDLR(-/-) mice. The adoptive transfer of an NKT cell-enriched splenocyte population from Valpha14Jalpha18 T-cell receptor transgenic mice resulted in a 73% increase in aortic root lesion area compared with recipients of NKT cell-deficient splenocytes derived from CD1d(-/-) mice after 12 weeks of Western-type diet feeding. The total serum from hypercholesterolemic mice leads to a small but significant activation of Valpha14Jalpha18 T-cell receptor-expressing hybridoma line by dendritic cells that is CD1d-dependent. Therefore, these studies demonstrate that NKT cells are proatherogenic in the absence of exogenous stimulation, and this activity is likely associated with endogenous lipid antigens carried by lipoproteins in the circulation and perhaps also in the atherosclerotic plaque.

  6. Characterization of the Natural Killer T-Cell Response in an Adoptive Transfer Model of Atherosclerosis

    PubMed Central

    VanderLaan, Paul A.; Reardon, Catherine A.; Sagiv, Yuval; Blachowicz, Lydia; Lukens, John; Nissenbaum, Michael; Wang, Chyung-Ru; Getz, Godfrey S.

    2007-01-01

    Natural killer T (NKT) cells have recently been implicated in atherogenesis, primarily for their ability to recognize and respond to lipid antigens. Because the atherosclerotic lesion is characterized by the retention and modification of lipids in the vascular wall, NKT cells may be involved in promoting the local vascular inflammatory response. Here, we investigate the proatherogenic role of NKT cells in an adoptive transfer model of atherosclerosis, using as recipients immune-deficient, atherosclerosis-susceptible RAG1−/−LDLR−/− mice. The adoptive transfer of an NKT cell-enriched splenocyte population from Vα14Jα18 T-cell receptor transgenic mice resulted in a 73% increase in aortic root lesion area compared with recipients of NKT cell-deficient splenocytes derived from CD1d−/− mice after 12 weeks of Western-type diet feeding. The total serum from hypercholesterolemic mice leads to a small but significant activation of Vα14Jα18 T-cell receptor-expressing hybridoma line by dendritic cells that is CD1d-dependent. Therefore, these studies demonstrate that NKT cells are proatherogenic in the absence of exogenous stimulation, and this activity is likely associated with endogenous lipid antigens carried by lipoproteins in the circulation and perhaps also in the atherosclerotic plaque. PMID:17322392

  7. In vivo imaging of T cell delivery to tumors after adoptive transfer therapy.

    PubMed

    Pittet, Mikael J; Grimm, Jan; Berger, Cedric R; Tamura, Takahiko; Wojtkiewicz, Gregory; Nahrendorf, Matthias; Romero, Pedro; Swirski, Filip K; Weissleder, Ralph

    2007-07-24

    Adoptive transfer therapy of in vitro-expanded tumor-specific cytolytic T lymphocytes (CTLs) can mediate objective cancer regression in patients. Yet, technical limitations hamper precise monitoring of posttherapy T cell responses. Here we show in a mouse model that fused single photon emission computed tomography and x-ray computed tomography allows quantitative whole-body imaging of (111)In-oxine-labeled CTLs at tumor sites. Assessment of CTL localization is rapid, noninvasive, three-dimensional, and can be repeated for longitudinal analyses. We compared the effects of lymphodepletion before adoptive transfer on CTL recruitment and report that combined treatment increased intratumoral delivery of CTLs and improved antitumor efficacy. Because (111)In-oxine is a Food and Drug Administration-approved clinical agent, and human SPECT-CT systems are available, this approach should be clinically translatable, insofar as it may assess the efficacy of immunization procedures in individual patients and lead to development of more effective therapies. PMID:17640914

  8. Systemic protein delivery by muscle-gene transfer is limited by a local immune response

    PubMed Central

    Wang, Lixin; Dobrzynski, Eric; Schlachterman, Alexander; Cao, Ou; Herzog, Roland W.

    2005-01-01

    Adeno-associated viral (AAV) vectors have been successfully used for therapeutic expression of systemic transgene products (such as factor IX or erythropoietin) following in vivo administration to skeletal muscle of animal models of inherited hematologic disorders. However, an immune response may be initiated if the transgene product represents a neoantigen. Here, we use ovalbumin (OVA) as a model antigen and demonstrate immune-mediated elimination of expression on muscle-directed AAV-2 gene transfer. Administration to immune competent mice resulted in transient systemic OVA expression. Within 10 days, OVA-specific T-helper cells had been activated in draining lymph nodes, an inflammatory immune response ensued, and OVA-expressing muscle fibers were destroyed by a cytotoxic CD8+ T-cell response. Use of a muscle-specific promoter did not prevent this immune response. Adoptively transferred CD4+ cells transgenic for a T-cell receptor specific to OVA peptide-major histocompatibility complex class II showed antigen-specific, vector dose-dependent proliferation confined to the draining lymph nodes of AAV-OVA–transduced muscle within 5 days after gene transfer and subsequently participated in lymphocytic infiltration of transduced muscle. This study documents that a local immune response limits sustained expression of a secreted protein in muscle gene transfer, a finding that may have consequences for design of clinical protocols. PMID:15713796

  9. Technical Considerations for the Generation of Adoptively Transferred T Cells in Cancer Immunotherapy.

    PubMed

    Visioni, Anthony; Skitzki, Joseph

    2016-01-01

    A significant function of the immune system is the surveillance and elimination of aberrant cells that give rise to cancer. Even when tumors are well established and metastatic, immune-mediated spontaneous regressions have been documented. While there are have been various forms of immunotherapy, one of the most widely studied for almost 40 years is adoptive cellular immunotherapy, but its success has yet to be fully realized. Adoptive cell transfer (ACT) is a therapeutic modality that has intrigued physicians and researchers for its many theoretical benefits. Preclinical investigations and human trials have utilized natural killer (NK) cells, dendritic cells (DC), macrophages, T-cells or B-cells for ACT with the most intense research focused on T-cell ACT. T-cells are exquisitely specific to the target of its T-cell receptor (TCR), thus potentially reducing the amount of collateral damage and off-target effects from treatment. T-cells also possess a memory subset that may reduce the risk of recurrence of a cancer after the successful treatment of the primary disease. There are several options for the source of T-cells used in the generation of cells for ACT. Perhaps the most widely known source is T-cells generated from tumor-infiltrating lymphocytes (TILs). However, studies have also employed peripheral blood mononuclear cells (PBMCs), lymph nodes, and even induced pluripotent stem cells (IPSCs) as a source of T-cells. Several important technical considerations exist regarding benefits and limitations of each source of T-cells. Unique aspects of T-cells factor into their ability to be efficacious in ACT including the total number of cells available for ACT, the anti-tumor efficacy on a per cell basis, the repertoire of TCRs specific to tumor cells, and their ability to traffic to various organs that harbor tumor. Current research is attempting to unlock the full potential of these cells to effectively and safely treat cancer. PMID:27657129

  10. Technical Considerations for the Generation of Adoptively Transferred T Cells in Cancer Immunotherapy

    PubMed Central

    Visioni, Anthony; Skitzki, Joseph

    2016-01-01

    A significant function of the immune system is the surveillance and elimination of aberrant cells that give rise to cancer. Even when tumors are well established and metastatic, immune-mediated spontaneous regressions have been documented. While there are have been various forms of immunotherapy, one of the most widely studied for almost 40 years is adoptive cellular immunotherapy, but its success has yet to be fully realized. Adoptive cell transfer (ACT) is a therapeutic modality that has intrigued physicians and researchers for its many theoretical benefits. Preclinical investigations and human trials have utilized natural killer (NK) cells, dendritic cells (DC), macrophages, T-cells or B-cells for ACT with the most intense research focused on T-cell ACT. T-cells are exquisitely specific to the target of its T-cell receptor (TCR), thus potentially reducing the amount of collateral damage and off-target effects from treatment. T-cells also possess a memory subset that may reduce the risk of recurrence of a cancer after the successful treatment of the primary disease. There are several options for the source of T-cells used in the generation of cells for ACT. Perhaps the most widely known source is T-cells generated from tumor-infiltrating lymphocytes (TILs). However, studies have also employed peripheral blood mononuclear cells (PBMCs), lymph nodes, and even induced pluripotent stem cells (IPSCs) as a source of T-cells. Several important technical considerations exist regarding benefits and limitations of each source of T-cells. Unique aspects of T-cells factor into their ability to be efficacious in ACT including the total number of cells available for ACT, the anti-tumor efficacy on a per cell basis, the repertoire of TCRs specific to tumor cells, and their ability to traffic to various organs that harbor tumor. Current research is attempting to unlock the full potential of these cells to effectively and safely treat cancer. PMID:27657129

  11. Auto-disable syringes for immunization: issues in technology transfer.

    PubMed Central

    Lloyd, J. S.; Milstien, J. B.

    1999-01-01

    WHO and its partners recommend the use of auto-disable syringes, "bundled" with the supply of vaccines when donor dollars are used, in all mass immunization campaigns, and also strongly advocate their use in routine immunization programmes. Because of the relatively high price of auto-disable syringes, WHO's Technical Network for Logistics in Health recommends that activities be initiated to encourage the transfer of production technology for these syringes as a means of promoting their use and enhancing access to the technology. The present article examines factors influencing technology transfer, including feasibility, corporate interest, cost, quality assurance, intellectual property considerations, and probable time frames for implementation. Technology transfer activities are likely to be complex and difficult, and may not result in lower prices for syringes. Guidelines are offered on technology transfer initiatives for auto-disable syringes to ensure the quality of the product, the reliability of the supply, and the feasibility of the technology transfer activity itself. PMID:10680248

  12. Lowest numbers of primary CD8(+) T cells can reconstitute protective immunity upon adoptive immunotherapy.

    PubMed

    Stemberger, Christian; Graef, Patricia; Odendahl, Marcus; Albrecht, Julia; Dössinger, Georg; Anderl, Florian; Buchholz, Veit R; Gasteiger, Georg; Schiemann, Matthias; Grigoleit, Götz U; Schuster, Friedhelm R; Borkhardt, Arndt; Versluys, Birgitta; Tonn, Torsten; Seifried, Erhard; Einsele, Hermann; Germeroth, Lothar; Busch, Dirk H; Neuenhahn, Michael

    2014-07-24

    Patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) are threatened by potentially lethal viral manifestations like cytomegalovirus (CMV) reactivation. Because the success of today's virostatic treatment is limited by side effects and resistance development, adoptive transfer of virus-specific memory T cells derived from the stem cell donor has been proposed as an alternative therapeutic strategy. In this context, dose minimization of adoptively transferred T cells might be warranted for the avoidance of graft-versus-host disease (GVHD), in particular in prophylactic settings after T-cell-depleting allo-HSCT protocols. To establish a lower limit for successful adoptive T-cell therapy, we conducted low-dose CD8(+) T-cell transfers in the well-established murine Listeria monocytogenes (L.m.) infection model. Major histocompatibility complex-Streptamer-enriched antigen-specific CD62L(hi) but not CD62L(lo) CD8(+) memory T cells proliferated, differentiated, and protected against L.m. infections after prophylactic application. Even progenies derived from a single CD62L(hi) L.m.-specific CD8(+) T cell could be protective against bacterial challenge. In analogy, low-dose transfers of Streptamer-enriched human CMV-specific CD8(+) T cells into allo-HSCT recipients led to strong pathogen-specific T-cell expansion in a compassionate-use setting. In summary, low-dose adoptive T-cell transfer (ACT) could be a promising strategy, particularly for prophylactic treatment of infectious complications after allo-HSCT.

  13. Measuring Immune Responses to recombinant AAV Gene Transfer

    PubMed Central

    Martino, Ashley T.; Herzog, Roland W.; Anegon, Ignacio; Adjali, Oumeya

    2013-01-01

    Following AAV-based gene transfer, the occurrence of adaptive immune responses specific to the vector or the transgene product is a major roadblock to successful clinical translation. These responses include antibodies against the AAV capsid, which can be neutralizing and therefore prevent the ability to repeatedly administer the vector, and CD8+ cytotoxic T lymphocytes, which can eliminate transduced cells. In addition, humans may have both humoral and cellular pre-existing immunity, as a result from natural infection with parent virus or related serotypes. The need for assays to detect and measure these anti-capsid immune responses in humans and in experimental animals is profound. Here, ELISPOT, immunocapture (ELISA), and neutralization assays are explained and provided in detail. Furthermore, such techniques can readily be adapted to monitor and quantify immune responses against therapeutic transgene products encoded by the vector genome. PMID:22034034

  14. Deletion of Plasmodium berghei-Specific CD4+ T Cells Adoptively Transferred into Recipient Mice after Challenge with Homologous Parasite

    NASA Astrophysics Data System (ADS)

    Hirunpetcharat, Chakrit; Good, Michael F.

    1998-02-01

    The immune response to malaria parasites includes T cell responses that reduce parasites by effector T cell responses and by providing help for antibody responses. Some parasites are more sensitive to antibody and others are more sensitive to cell-mediated immunity. We demonstrate that cultured CD4+ T cells that produce interferon CD4+ and interleukin 2, but not interleukin 4, in response to stimulation with the rodent parasite Plasmodium berghei can reduce but not eliminate parasites in vivo after adoptive transfer. Although cells can persist in vivo for up to 9 months in uninfected mice, infection results in elimination of up to 99% of specific T cells in different tissues, as judged by tracking T cells labeled with the fluorescent dye 5-(and-6)-carboxyfluorescein diacetate succinimidyl ester. T cells specific for ovalbumin are unaffected. In vivo activation and division of transferred T cells per se are not responsible for deletion because T cells positive for 5-(and -6)-carboxyfluorescein diacetate succinimidyl ester divide up to six times within 7 days in uninfected mice and are not deleted. Understanding the factors responsible for parasite-mediated specific deletion of T cells would enhance our knowledge of parasite immunity.

  15. Targeting Stat3 in the myeloid compartment drastically improves the in vivo antitumor functions of adoptively transferred T cells

    PubMed Central

    Herrmann, Andreas; Kortylewski, Marcin; Kujawski, Maciej; Zhang, Chunyan; Reckamp, Karen; Armstrong, Brian; Wang, Lin; Kowolik, Claudia; Deng, Jiehui; Robert, Figlin; Yu, Hua

    2010-01-01

    Improving effector T cell functions is highly desirable for preventive or therapeutic interventions of diverse diseases. Stat3 in the myeloid compartment constrains Th-1 type immunity, dampening natural and induced antitumor immune responses. We have recently developed an in vivo siRNA delivery platform by conjugating a TLR9 agonist with siRNA that efficiently targets myeloid and B cells. Here we show that either ablating the Stat3 alleles in the myeloid compartment and B cells combined with CpG triggering or administrating the CpG-Stat3siRNA conjugates drastically augments effector functions of adoptively transferred CD8+ T cells. Specifically, we demonstrate that both approaches are capable of increasing dendritic cell and CD8+ T cell engagement in tumor draining lymph nodes. Furthermore, both approaches can significantly activate the transferred CD8+ T cells in vivo, upregulating effector molecules such as perforin, granzyme B and IFN-γ. Intravital multiphoton microscopy reveals that Stat3 silencing combined with CpG triggering greatly increases killing activity and tumor infiltration of transferred T cells. These results suggest the use of CpG-Stat3siRNA, and possibly other Stat3 inhibitors, as a potent adjuvant to improve T cell therapies. PMID:20841481

  16. Improving the outcome of adoptive cell transfer by targeting tumor escape.

    PubMed

    Kaluza, Karen M; Vile, Richard

    2013-01-01

    Adoptive T-cell transfer is among the most promising immunotherapies against cancer. To continue increasing the potential of this therapy, our studies focus on the inhibition of tumor recurrence. Recently, we have demonstrated several ways in which combination therapies involving multiple T-cell populations and immunostimulatory chemotherapy can enhance long-term survival.

  17. Cellular Immune Response Against Firefly Luciferase After Sleeping Beauty–Mediated Gene Transfer In Vivo

    PubMed Central

    Podetz-Pedersen, Kelly M.; Vezys, Vaiva; Somia, Nikunj V.; Russell, Stephen J.

    2014-01-01

    Abstract The Sleeping Beauty (SB) transposon system has been shown to mediate new gene sequence integration resulting in long-term expression. Here the effectiveness of hyperactive SB100X transposase was tested, and we found that hydrodynamic co-delivery of a firefly luciferase transposon (pT2/CaL) along with SB100X transposase (pCMV-SB100X) resulted in remarkably sustained, high levels of luciferase expression. However, after 4 weeks there was a rapid, animal-by-animal loss of luciferase expression that was not observed in immunodeficient mice. We hypothesized that this sustained, high-level luciferase expression achieved using the SB100X transposase elicits an immune response in pT2/CaL co-administered mice, which was supported by the rapid loss of luciferase expression upon challenge of previously treated animals and in naive animals adoptively transferred with splenocytes from previously treated animals. Specificity of the immune response to luciferase was demonstrated by increased cytokine expression in splenocytes after exposure to luciferase peptide in parallel with MHC I–luciferase peptide tetramer binding. This anti-luciferase immune response observed following continuous, high-level luciferase expression in vivo clearly impacts its use as an in vivo reporter. As both an immunogen and an extremely sensitive reporter, luciferase is also a useful model system for the study of immune responses following in vivo gene transfer and expression. PMID:25093708

  18. Passive immunization against HIV/AIDS by antibody gene transfer.

    PubMed

    Yang, Lili; Wang, Pin

    2014-01-27

    Despite tremendous efforts over the course of many years, the quest for an effective HIV vaccine by the classical method of active immunization remains largely elusive. However, two recent studies in mice and macaques have now demonstrated a new strategy designated as Vectored ImmunoProphylaxis (VIP), which involves passive immunization by viral vector-mediated delivery of genes encoding broadly neutralizing antibodies (bnAbs) for in vivo expression. Robust protection against virus infection was observed in preclinical settings when animals were given VIP to express monoclonal neutralizing antibodies. This unorthodox approach raises new promise for combating the ongoing global HIV pandemic. In this article, we survey the status of antibody gene transfer, review the revolutionary progress on isolation of extremely bnAbs, detail VIP experiments against HIV and its related virus conduced in humanized mice and macaque monkeys, and discuss the pros and cons of VIP and its opportunities and challenges towards clinical applications to control HIV/AIDS endemics.

  19. Adoptive transfer of helminth antigen-pulsed dendritic cells protects against the development of experimental colitis in mice.

    PubMed

    Matisz, Chelsea E; Leung, Gabriella; Reyes, Jose Luis; Wang, Arthur; Sharkey, Keith A; McKay, Derek M

    2015-11-01

    Infection with helminth parasites and treatment with worm extracts can suppress inflammatory disease, including colitis. Postulating that dendritic cells (DCs) participated in the suppression of inflammation and seeking to move beyond the use of helminths per se, we tested the ability of Hymenolepis diminuta antigen-pulsed DCs to suppress colitis as a novel cell-based immunotherapy. Bone marrow derived DCs pulsed with H. diminuta antigen (HD-DCs), or PBS-, BSA-, or LPS-DCs as controls, were transferred into wild-type (WT), interleukin-10 (IL-10) knock-out (KO), and RAG-1 KO mice, and the impact on dinitrobenzene sulphonic acid (DNBS)-induced colitis and splenic cytokine production assessed 72 h later. Mice receiving HD-DCs were significantly protected from DNBS-induced colitis and of the experimental groups only these mice displayed increased Th2 cytokines and IL-10 production. Adoptive transfer of HD-DCs protected neither RAG-1 nor IL-10 KO mice from DNBS-colitis. Furthermore, the transfer of CD4(+) splenocytes from recipients of HD-DCs protected naïve mice against DNBS-colitis, in an IL-10 dependent manner. Thus, HD-DCs are a novel anti-colitic immunotherapy that can educate anti-colitic CD4(+) T cells: mechanistically, the anti-colitic effect of HD-DCs requires that the host has an adaptive immune response and the ability to mobilize IL-10.

  20. Effect of Adoptive Transfer or Depletion of Regulatory T Cells on Triptolide-induced Liver Injury

    PubMed Central

    Wang, Xinzhi; Sun, Lixin; Zhang, Luyong; Jiang, Zhenzhou

    2016-01-01

    Objective: The aim of this study is to clarify the role of regulatory T cell (Treg) in triptolide (TP)-induced hepatotoxicity. Methods: Female C57BL/6 mice received either adoptive transfer of Tregs or depletion of Tregs, then underwent TP administration and were sacrificed 24 h after TP administration. Liver injury was determined according to alanine transaminase (ALT) and aspartate transaminase (AST) levels in serum and histopathological change in liver tissue. Hepatic frequencies of Treg cells and the mRNA expression levels of transcription factor Forkhead box P3 and retinoid orphan nuclear receptor γt (RORγt), interleukin-10 (IL-10), suppressor of cytokine signaling (SOCS), and Notch/Notch ligand were investigated. Results: During TP-induced liver injury, hepatic Treg and IL-10 decreased, while T helper 17 cells cell-transcription factor RORγt, SOCS and Notch signaling increased, accompanied with liver inflammation. Adoptive transfer of Tregs ameliorated the severity of TP-induced liver injury, accompanied with increased levels of hepatic Treg and IL-10. Adoptive transfer of Tregs remarkably inhibited the expression of RORγt, SOCS3, Notch1, and Notch3. On the contrary, depletion of Treg cells in TP-administered mice resulted in a notable increase of RORγt, SOCS1, SOCS3, and Notch3, while the Treg and IL-10 of liver decreased. Consistent with the exacerbation of liver injury, higher serum levels of ALT and AST were detected in Treg-depleted mice. Conclusion: These results showed that adoptive transfer or depletion of Tregs attenuated or aggravated TP-induced liver injury, suggesting that Tregs could play important roles in the progression of liver injury. SOCS proteins and Notch signaling affected Tregs, which may contribute to the pathogenesis of TP-induced hepatotoxicity. PMID:27148057

  1. Anti-Tumor Effects after Adoptive Transfer of IL-12 Transposon-Modified Murine Splenocytes in the OT-I-Melanoma Mouse Model.

    PubMed

    Galvan, Daniel L; O'Neil, Richard T; Foster, Aaron E; Huye, Leslie; Bear, Adham; Rooney, Cliona M; Wilson, Matthew H

    2015-01-01

    Adoptive transfer of gene modified T cells provides possible immunotherapy for patients with cancers refractory to other treatments. We have previously used the non-viral piggyBac transposon system to gene modify human T cells for potential immunotherapy. However, these previous studies utilized adoptive transfer of modified human T cells to target cancer xenografts in highly immunodeficient (NOD-SCID) mice that do not recapitulate an intact immune system. Currently, only viral vectors have shown efficacy in permanently gene-modifying mouse T cells for immunotherapy applications. Therefore, we sought to determine if piggyBac could effectively gene modify mouse T cells to target cancer cells in a mouse cancer model. We first demonstrated that we could gene modify cells to express murine interleukin-12 (p35/p40 mIL-12), a transgene with proven efficacy in melanoma immunotherapy. The OT-I melanoma mouse model provides a well-established T cell mediated immune response to ovalbumin (OVA) positive B16 melanoma cells. B16/OVA melanoma cells were implanted in wild type C57Bl6 mice. Mouse splenocytes were isolated from C57Bl6 OT-I mice and were gene modified using piggyBac to express luciferase. Adoptive transfer of luciferase-modified OT-I splenocytes demonstrated homing to B16/OVA melanoma tumors in vivo. We next gene-modified OT-I cells to express mIL-12. Adoptive transfer of mIL-12-modified mouse OT-I splenocytes delayed B16/OVA melanoma tumor growth in vivo compared to control OT-I splenocytes and improved mouse survival. Our results demonstrate that the piggyBac transposon system can be used to gene modify splenocytes and mouse T cells for evaluating adoptive immunotherapy strategies in immunocompetent mouse tumor models that may more directly mimic immunotherapy applications in humans. PMID:26473608

  2. Anti-Tumor Effects after Adoptive Transfer of IL-12 Transposon-Modified Murine Splenocytes in the OT-I-Melanoma Mouse Model

    PubMed Central

    Foster, Aaron E.; Huye, Leslie; Bear, Adham; Rooney, Cliona M.; Wilson, Matthew H.

    2015-01-01

    Adoptive transfer of gene modified T cells provides possible immunotherapy for patients with cancers refractory to other treatments. We have previously used the non-viral piggyBac transposon system to gene modify human T cells for potential immunotherapy. However, these previous studies utilized adoptive transfer of modified human T cells to target cancer xenografts in highly immunodeficient (NOD-SCID) mice that do not recapitulate an intact immune system. Currently, only viral vectors have shown efficacy in permanently gene-modifying mouse T cells for immunotherapy applications. Therefore, we sought to determine if piggyBac could effectively gene modify mouse T cells to target cancer cells in a mouse cancer model. We first demonstrated that we could gene modify cells to express murine interleukin-12 (p35/p40 mIL-12), a transgene with proven efficacy in melanoma immunotherapy. The OT-I melanoma mouse model provides a well-established T cell mediated immune response to ovalbumin (OVA) positive B16 melanoma cells. B16/OVA melanoma cells were implanted in wild type C57Bl6 mice. Mouse splenocytes were isolated from C57Bl6 OT-I mice and were gene modified using piggyBac to express luciferase. Adoptive transfer of luciferase-modified OT-I splenocytes demonstrated homing to B16/OVA melanoma tumors in vivo. We next gene-modified OT-I cells to express mIL-12. Adoptive transfer of mIL-12-modified mouse OT-I splenocytes delayed B16/OVA melanoma tumor growth in vivo compared to control OT-I splenocytes and improved mouse survival. Our results demonstrate that the piggyBac transposon system can be used to gene modify splenocytes and mouse T cells for evaluating adoptive immunotherapy strategies in immunocompetent mouse tumor models that may more directly mimic immunotherapy applications in humans. PMID:26473608

  3. Antiangiogenic immunotherapy targeting Flk-1, DNA vaccine and adoptive T cell transfer, inhibits ocular neovascularization

    SciTech Connect

    Zhang, Han; Sonoda, Koh-Hei; Hijioka, Kuniaki; Qiao, Hong; Oshima, Yuji; Ishibashi, Tatsuro

    2009-04-17

    Ocular neovascularization (NV) is the primary cause of blindness in a wide range of ocular diseases. The exact mechanism underlying the pathogenesis of ocular NV is not yet well understood, and so there is no satisfactory therapy for ocular NV. Here, we describe a strategy targeting Flk-1, a self-antigen overexpressed on proliferating endothelial cells in ocular NV, by antiangiogenic immunotherapy-DNA vaccine and adoptive T cell therapy. An oral DNA vaccine encoding Flk-1 carried by attenuated Salmonella typhimurium markedly suppressed development of laser-induced choroidal NV. We further demonstrated that adoptive transfer of vaccine-induced CD8{sup +} T cells reduced pathological preretinal NV, with a concomitant facilitation of physiological revascularization after oxygen-induced retinal vessel obliteration. However, physiological retinal vascular development was unaffected in neonatal mice transferred with vaccine-induced CD8{sup +} T cells. These findings suggested that antiangiogenic immunotherapy targeting Flk-1 such as vaccination and adoptive immunotherapy may contribute to future therapies for ocular NV.

  4. Transferred interbacterial antagonism genes augment eukaryotic innate immune function.

    PubMed

    Chou, Seemay; Daugherty, Matthew D; Peterson, S Brook; Biboy, Jacob; Yang, Youyun; Jutras, Brandon L; Fritz-Laylin, Lillian K; Ferrin, Michael A; Harding, Brittany N; Jacobs-Wagner, Christine; Yang, X Frank; Vollmer, Waldemar; Malik, Harmit S; Mougous, Joseph D

    2015-02-01

    Horizontal gene transfer allows organisms to rapidly acquire adaptive traits. Although documented instances of horizontal gene transfer from bacteria to eukaryotes remain rare, bacteria represent a rich source of new functions potentially available for co-option. One benefit that genes of bacterial origin could provide to eukaryotes is the capacity to produce antibacterials, which have evolved in prokaryotes as the result of eons of interbacterial competition. The type VI secretion amidase effector (Tae) proteins are potent bacteriocidal enzymes that degrade the cell wall when delivered into competing bacterial cells by the type VI secretion system. Here we show that tae genes have been transferred to eukaryotes on at least six occasions, and that the resulting domesticated amidase effector (dae) genes have been preserved for hundreds of millions of years through purifying selection. We show that the dae genes acquired eukaryotic secretion signals, are expressed within recipient organisms, and encode active antibacterial toxins that possess substrate specificity matching extant Tae proteins of the same lineage. Finally, we show that a dae gene in the deer tick Ixodes scapularis limits proliferation of Borrelia burgdorferi, the aetiologic agent of Lyme disease. Our work demonstrates that a family of horizontally acquired toxins honed to mediate interbacterial antagonism confers previously undescribed antibacterial capacity to eukaryotes. We speculate that the selective pressure imposed by competition between bacteria has produced a reservoir of genes encoding diverse antimicrobial functions that are tailored for co-option by eukaryotic innate immune systems. PMID:25470067

  5. Myeloid-derived suppressor cell impact on endogenous and adoptively transferred T cells.

    PubMed

    Arina, Ainhoa; Bronte, Vincenzo

    2015-04-01

    Novel models of autochthonous tumorigenesis and adoptive T cell therapy (ATT) are providing new clues regarding the pro-tumorigenic and immunosuppressive effects of myeloid-derived suppressor cells (MDSC), and their interaction with T cells. New findings are shifting the perception of the main level at which MDSC act, from direct cell-to-cell suppression to others, such as limiting T cell infiltration. Adoptively transferred, high-avidity T cells recognizing peptides with high-affinity for MHC-I eliminated large tumors. However, low-avidity T cells or low-affinity peptides resulted in failure to eradicate tumors. Manipulation of intratumoral myeloid cells improved the outcome of otherwise unsuccessful ATT. Therefore, therapeutic intervention directed at the tumor stroma might be required when using suboptimal T cells for ATT.

  6. On the optimization of the generalized coplanar Hohmann impulsive transfer adopting energy change concept

    NASA Astrophysics Data System (ADS)

    Kamel, Osman M.; Soliman, Adel S.

    2005-02-01

    We considered the problem of transferring the rocket's orbit to higher energy orbit, using minimum fuel cost, as a problem in change of energy, since this is most convenient. For the generalized Hohmann case (the departure; the transferring and the destination orbits are ellipses), we adopt the first configuration only, when the apogee of transfer orbit, and the apogee of destination orbit are coincident. Firstly, we assign the ΔvA, ΔvB increments in velocity at points A,B (the position of peri-apse and apo-apse impulses respectively), as functions of the eccentricity of the transfer orbit, eT. Subsequently, we apply the optimum condition leading to the derivation of the quartic equation in eT, and showed how to deduce (ΔvA+ΔvB)Min. A numerical example is presented, in which we determined the four roots of the quartic equation, by a numerical Mathematica Version 2.2. We selected the adequate consistent root, only one in this case, and evaluated (ΔvA+ΔvB)Min for the two orbits of the couple Earth and Mars. This article is a new approach and leads to new discoveries involved in the problem, consequently adds new insight and avoids complexities of previous procedures.

  7. Adoptive transfer of Mammaglobin-A epitope specific CD8 T cells combined with a single low dose of total body irradiation eradicates breast tumors.

    PubMed

    Lerret, Nadine M; Rogozinska, Magdalena; Jaramillo, Andrés; Marzo, Amanda L

    2012-01-01

    Adoptive T cell therapy has proven to be beneficial in a number of tumor systems by targeting the relevant tumor antigen. The tumor antigen targeted in our model is Mammaglobin-A, expressed by approximately 80% of human breast tumors. Here we evaluated the use of adoptively transferred Mammaglobin-A specific CD8 T cells in combination with low dose irradiation to induce breast tumor rejection and prevent relapse. We show Mammaglobin-A specific CD8 T cells generated by DNA vaccination with all epitopes (Mammaglobin-A2.1, A2.2, A2.4 and A2.6) and full-length DNA in vivo resulted in heterogeneous T cell populations consisting of both effector and central memory CD8 T cell subsets. Adoptive transfer of spleen cells from all Mammaglobin-A2 immunized mice into tumor-bearing SCID/beige mice induced tumor regression but this anti-tumor response was not sustained long-term. Additionally, we demonstrate that only the adoptive transfer of Mammaglobin-A2 specific CD8 T cells in combination with a single low dose of irradiation prevents tumors from recurring. More importantly we show that this single dose of irradiation results in the down regulation of the macrophage scavenger receptor 1 on dendritic cells within the tumor and reduces lipid uptake by tumor resident dendritic cells potentially enabling the dendritic cells to present tumor antigen more efficiently and aid in tumor clearance. These data reveal the potential for adoptive transfer combined with a single low dose of total body irradiation as a suitable therapy for the treatment of established breast tumors and the prevention of tumor recurrence.

  8. Adoptive transfer of cytotoxic T lymphocytes targeting two different antigens limits antigen loss and tumor escape.

    PubMed

    Kaluza, Karen M; Kottke, Timothy; Diaz, Rosa Maria; Rommelfanger, Diana; Thompson, Jill; Vile, Richard

    2012-10-01

    An antitumor T-cell response can lead to tumor control without clearing all tumor cells. As long as residual tumor cells remain, there is a constant risk of escape from that T-cell response. We previously showed that adoptive transfer of anti-ova OT-I T cells into B16ova-bearing mice led to tumor regression followed by escape of tumors that had lost the ova gene, rendering the OT-I T cells ineffective. In this study, we hypothesized that simultaneous transfer of cytotoxic T lymphocytes targeted against two independent antigens would reduce selection for single-antigen-loss cells, thereby limiting tumor escape. Using OT-I and Pmel T cells to treat B16ova tumors, we found that early cotransfer could prevent tumor emergence in most mice, whereas neither T-cell specificity alone was able to do so. When combined with total body irradiation for the treatment of larger 7-day tumors, cotransfer was also better at limiting tumor recurrence, and the tumors that did escape combination therapy continued to express both target antigens. As adoptively transferred T cells also persisted in vivo, even in mice with recurrent tumors, we hypothesized that restimulation of these antitumor T cells would prolong survival of mice with recurrent tumors. Consistent with this hypothesis, administration of a low-dose regimen of cyclophosphamide following tumor escape slowed tumor growth in mice that had previously received T-cell therapy, but not in control-treated mice, an effect that was associated with increased activation of T cells in vitro by low- but not high-dose cyclophosphamide.

  9. Experimental Salmonellosis VI. In Vitro Transfer of Cellular Immunity of Mouse Mononuclear Phagocytes

    PubMed Central

    Saito, Kazuko; Mitsuhashi, Susumu

    1965-01-01

    Saito, Kazuko (Gunma University, Maebashi, Japan), and Susumu Mitsuhashi. Experimental salmonellosis. VI. In vitro transfer of cellular immunity of mouse mononuclear phagocytes. J. Bacteriol. 90:629–634. 1965.—A culture medium of the mononuclear phagocytes (monocytes) of mice immunized with live vaccine of Salmonella enteritidis contains the transfer agent (TA) of cellular immunity from immune to non-immune monocytes. The TA is of ribonucleic acid nature, is nondialyzable through cellophane, and maintains its active state for 3 months in a frozen state (−10 C) and for 24 hr at 37 C. PMID:16562059

  10. Modulation of tumor response to photodynamic therapy in severe combined immunodeficient (SCID) mice by adoptively transferred lymphoid cells

    NASA Astrophysics Data System (ADS)

    Korbelik, Mladen; Krosl, Gorazd; Krosl, Jana; Dougherty, Graeme J.

    1996-04-01

    Photodynamic treatment, consisting of intravenous injection of PhotofrinR (10 mg/kg) followed by exposure to 110 J/cm2 of 630 plus or minus 10 nm light 24 hours later, cured 100% of EMT6 tumors (murine mammary sarcoma) growing in syngeneic immunocompetent BALB/C mice. In contrast, the same treatment produced no cures of EMT6 tumors growing in either nude or SCID mice (immunodeficient strains). EMT6 tumors growing in BALB/C and SCID mice showed no difference in either the level of PhotofrinR accumulated per gram of tumor tissue, or the extent of tumor cell killing during the first 24 hours post photodynamic therapy (PDT). In an attempt to improve the sensitivity to PDT of EMT6 tumors growing in SCID mice, these hosts were given either splenic T lymphocytes or whole bone marrow from BALB/C mice. The adoptive transfer of lymphocytes 9 days before PDT was successful in delaying tumor recurrence but produced no cures. A better improvement in PDT response was obtained with tumors growing in SCID mice reconstituted with BALB/C bone marrow (tumor cure rate of 63%). The results of this study demonstrate that, at least with the EMT6 tumor model, antitumor immune activity mediated by lymphoid cell populations makes an important contribution to the curative effect of PDT.

  11. Evaluation of the Therapeutic Potential of Bone Marrow-Derived Myeloid Suppressor Cell (MDSC) Adoptive Transfer in Mouse Models of Autoimmunity and Allograft Rejection

    PubMed Central

    Bouchet-Delbos, Laurence; Beriou, Gaelle; Merieau, Emmanuel; Hill, Marcelo; Delneste, Yves; Cuturi, Maria Cristina; Louvet, Cedric

    2014-01-01

    Therapeutic use of immunoregulatory cells represents a promising approach for the treatment of uncontrolled immunity. During the last decade, myeloid-derived suppressor cells (MDSC) have emerged as novel key regulatory players in the context of tumor growth, inflammation, transplantation or autoimmunity. Recently, MDSC have been successfully generated in vitro from naive mouse bone marrow cells or healthy human PBMCs using minimal cytokine combinations. In this study, we aimed to evaluate the potential of adoptive transfer of such cells to control auto- and allo-immunity in the mouse. Culture of bone marrow cells with GM-CSF and IL-6 consistently yielded a majority of CD11b+Gr1hi/lo cells exhibiting strong inhibition of CD8+ T cell proliferation in vitro. However, adoptive transfer of these cells failed to alter antigen-specific CD8+ T cell proliferation and cytotoxicity in vivo. Furthermore, MDSC could not prevent the development of autoimmunity in a stringent model of type 1 diabetes. Rather, loading the cells prior to injection with a pancreatic neo-antigen peptide accelerated the development of the disease. Contrastingly, in a model of skin transplantation, repeated injection of MDSC or single injection of LPS-activated MDSC resulted in a significant prolongation of allograft survival. The beneficial effect of MDSC infusions on skin graft survival was paradoxically not explained by a decrease of donor-specific T cell response but associated with a systemic over-activation of T cells and antigen presenting cells, prominently in the spleen. Taken together, our results indicate that in vitro generated MDSC bear therapeutic potential but will require additional in vitro factors or adjunct immunosuppressive treatments to achieve safe and more robust immunomodulation upon adoptive transfer. PMID:24927018

  12. Adoptive Transfer of Dendritic Cells Expressing Fas Ligand Modulates Intestinal Inflammation in a Model of Inflammatory Bowel Disease

    PubMed Central

    de Jesus, Edelmarie Rivera; Isidro, Raymond A; Cruz, Myrella L; Marty, Harry; Appleyard, Caroline B

    2016-01-01

    Background Inflammatory bowel diseases (IBD) are chronic relapsing inflammatory conditions of unknown cause and likely result from the loss of immunological tolerance, which leads to over-activation of the gut immune system. Gut macrophages and dendritic cells (DCs) are essential for maintaining tolerance, but can also contribute to the inflammatory response in conditions such as IBD. Current therapies for IBD are limited by high costs and unwanted toxicities and side effects. The possibility of reducing intestinal inflammation with DCs genetically engineered to over-express the apoptosis-inducing FasL (FasL-DCs) has not yet been explored. Objective Investigate the immunomodulatory effect of administering FasL-DCs in the rat trinitrobenzene sulfonic acid (TNBS) model of acute colitis. Methods Expression of FasL on DCs isolated from the mesenteric lymph nodes (MLNs) of normal and TNBS-colitis rats was determined by flow cytometry. Primary rat bone marrow DCs were transfected with rat FasL plasmid (FasL-DCs) or empty vector (EV-DCs). The effect of these DCs on T cell IFNγ secretion and apoptosis was determined by ELISPOT and flow cytometry for Annexin V, respectively. Rats received FasL-DCs or EV-DCs intraperitoneally 96 and 48 hours prior to colitis induction with TNBS. Colonic T cell and neutrophil infiltration was determined by immunohistochemistry for CD3 and myeloperoxidase activity assay, respectively. Macrophage number and phenotype was measured by double immunofluorescence for CD68 and inducible Nitric Oxide Synthase. Results MLN dendritic cells from normal rats expressed more FasL than those from colitic rats. Compared to EV-DCs, FasL-DCs reduced T cell IFNγ secretion and increased T cell apoptosis in vitro. Adoptive transfer of FasL-DCs decreased macroscopic and microscopic damage scores and reduced colonic T cells, neutrophils, and proinflammatory macrophages when compared to EV-DC adoptive transfer. Conclusion FasL-DCs are effective at treating colonic

  13. Relationship between maternal transfer of immunity and mother fecundity in an insect.

    PubMed

    Zanchi, C; Troussard, J-P; Moreau, J; Moret, Y

    2012-08-22

    Trans-generational immune priming (TGIP) corresponds to the plastic adjustment of offspring immunity as a result of maternal immune experience. TGIP is expected to improve mother's fitness by improving offspring individual performance in an environment where parasitism becomes more prevalent. However, it was recently demonstrated that maternal transfer of immunity to the offspring is costly for immune-challenged female insects. Thus, these females might not provide immune protection to all their offspring because of the inherent cost of other fitness-related traits. Females are therefore expected to adjust their investment to individual offspring immune protection in ways that maximize their fitness. In this study, we investigated how bacterially immune-challenged females of the mealworm beetle, Tenebrio molitor, provision their eggs with immune protection according to egg production. We found that immune-challenged females provide a variable number of their eggs with internal antibacterial activity along egg-laying bouts. Furthermore, within the first immune-protected egg-laying bout (2-4 days after the maternal immune challenge), the number of eggs protected was strongly dependent on the number of eggs produced. Immune-challenged females might therefore adjust their investment into TGIP and fecundity according of their individual perception of the risk of dying from the infection and the expected parasitic conditions for the offspring.

  14. Relationship between maternal transfer of immunity and mother fecundity in an insect.

    PubMed

    Zanchi, C; Troussard, J-P; Moreau, J; Moret, Y

    2012-08-22

    Trans-generational immune priming (TGIP) corresponds to the plastic adjustment of offspring immunity as a result of maternal immune experience. TGIP is expected to improve mother's fitness by improving offspring individual performance in an environment where parasitism becomes more prevalent. However, it was recently demonstrated that maternal transfer of immunity to the offspring is costly for immune-challenged female insects. Thus, these females might not provide immune protection to all their offspring because of the inherent cost of other fitness-related traits. Females are therefore expected to adjust their investment to individual offspring immune protection in ways that maximize their fitness. In this study, we investigated how bacterially immune-challenged females of the mealworm beetle, Tenebrio molitor, provision their eggs with immune protection according to egg production. We found that immune-challenged females provide a variable number of their eggs with internal antibacterial activity along egg-laying bouts. Furthermore, within the first immune-protected egg-laying bout (2-4 days after the maternal immune challenge), the number of eggs protected was strongly dependent on the number of eggs produced. Immune-challenged females might therefore adjust their investment into TGIP and fecundity according of their individual perception of the risk of dying from the infection and the expected parasitic conditions for the offspring. PMID:22535782

  15. Adoptive immunity mediated by HLA-A*0201 restricted Asp f16 peptides-specific CD8+ T cells against Aspergillus fumigatus infection.

    PubMed

    Sun, Z; Zhu, P; Li, L; Wan, Z; Zhao, Z; Li, R

    2012-11-01

    Aspergillus fumigatus (A. fumigatus) is the most common pathogen of invasive aspergillosis (IA), a life-threatening infection in immunocompromised patients. Recent findings revealed that CD8+ T cells can mediate cytotoxic activity against A. fumigatus. Here, we bioinformatically identified three HLA-A*0201-restricted peptides from Asp f16, an A. fumigatus antigen which was previously shown to be involved in T cell immunity. Our immunological results demonstrated that these peptides can potently induce cytotoxic T lymphocyte (CTL) response in CD8+ T cells, thus, damaging the conidia and hyphae of A. fumigatus. Moreover, the Asp f16 peptides can also raise Th1 cell-like response, as measured by interferon-γ (IFN-γ) enzyme-linked immunosorbent spot (ELISPOT). Furthermore, we established an invasive pulmonary aspergillosis model in HLA-A*0201 transgenic mice. Adoptive transfer of Asp f16 peptides-specific CTL significantly extended the overall survival time in the A. fumigatus-infected immunocompromised mice. In conclusion, our results demonstrate that the Asp f16 peptides might provide immunity against invasive A. fumigatus infection.

  16. Transfer of Maternal Antimicrobial Immunity to HIV-Exposed Uninfected Newborns.

    PubMed

    Abu-Raya, Bahaa; Smolen, Kinga K; Willems, Fabienne; Kollmann, Tobias R; Marchant, Arnaud

    2016-01-01

    The transfer of maternal immune factors to the newborn is critical for protection from infectious disease in early life. Maternally acquired passive immunity provides protection until the infant is beyond early life's increased susceptibility to severe infections or until active immunity is achieved following infant's primary immunization. However, as reviewed here, human immunodeficiency virus (HIV) infection alters the transfer of immune factors from HIV-infected mothers to the HIV-exposed newborns and young infants. This may relate to the immune activation in HIV-infected pregnant women, associated with the production of inflammatory cytokines at the maternofetal interface associated with inflammatory responses in the newborn. We also summarize mother-targeting interventions to improve the health of infants born to HIV-infected women, such as immunization during pregnancy and reduction of maternal inflammation. Maternal immunization offers the potential to compensate for the decreased transplacentally transferred maternal antibodies observed in HIV-exposed infants. Current data suggest reduced immunogenicity of vaccines in HIV-infected pregnant women, possibly reducing the protective impact of maternal immunization for HIV-exposed infants. Fortunately, levels of antibodies appear preserved in the breast milk of HIV-infected women, which supports the recommendation to breast-feed during antiretroviral treatment to protect HIV-exposed infants. PMID:27630640

  17. Transfer of Maternal Antimicrobial Immunity to HIV-Exposed Uninfected Newborns

    PubMed Central

    Abu-Raya, Bahaa; Smolen, Kinga K.; Willems, Fabienne; Kollmann, Tobias R.; Marchant, Arnaud

    2016-01-01

    The transfer of maternal immune factors to the newborn is critical for protection from infectious disease in early life. Maternally acquired passive immunity provides protection until the infant is beyond early life’s increased susceptibility to severe infections or until active immunity is achieved following infant’s primary immunization. However, as reviewed here, human immunodeficiency virus (HIV) infection alters the transfer of immune factors from HIV-infected mothers to the HIV-exposed newborns and young infants. This may relate to the immune activation in HIV-infected pregnant women, associated with the production of inflammatory cytokines at the maternofetal interface associated with inflammatory responses in the newborn. We also summarize mother-targeting interventions to improve the health of infants born to HIV-infected women, such as immunization during pregnancy and reduction of maternal inflammation. Maternal immunization offers the potential to compensate for the decreased transplacentally transferred maternal antibodies observed in HIV-exposed infants. Current data suggest reduced immunogenicity of vaccines in HIV-infected pregnant women, possibly reducing the protective impact of maternal immunization for HIV-exposed infants. Fortunately, levels of antibodies appear preserved in the breast milk of HIV-infected women, which supports the recommendation to breast-feed during antiretroviral treatment to protect HIV-exposed infants.

  18. Transfer of Maternal Antimicrobial Immunity to HIV-Exposed Uninfected Newborns

    PubMed Central

    Abu-Raya, Bahaa; Smolen, Kinga K.; Willems, Fabienne; Kollmann, Tobias R.; Marchant, Arnaud

    2016-01-01

    The transfer of maternal immune factors to the newborn is critical for protection from infectious disease in early life. Maternally acquired passive immunity provides protection until the infant is beyond early life’s increased susceptibility to severe infections or until active immunity is achieved following infant’s primary immunization. However, as reviewed here, human immunodeficiency virus (HIV) infection alters the transfer of immune factors from HIV-infected mothers to the HIV-exposed newborns and young infants. This may relate to the immune activation in HIV-infected pregnant women, associated with the production of inflammatory cytokines at the maternofetal interface associated with inflammatory responses in the newborn. We also summarize mother-targeting interventions to improve the health of infants born to HIV-infected women, such as immunization during pregnancy and reduction of maternal inflammation. Maternal immunization offers the potential to compensate for the decreased transplacentally transferred maternal antibodies observed in HIV-exposed infants. Current data suggest reduced immunogenicity of vaccines in HIV-infected pregnant women, possibly reducing the protective impact of maternal immunization for HIV-exposed infants. Fortunately, levels of antibodies appear preserved in the breast milk of HIV-infected women, which supports the recommendation to breast-feed during antiretroviral treatment to protect HIV-exposed infants. PMID:27630640

  19. Transfer and adoption of advanced information technology solutions in resource-poor environments: the case of telemedicine systems adoption in Ethiopia.

    PubMed

    Kifle, Mengistu; Payton, Fay Cobb; Mbarika, Victor; Meso, Peter

    2010-04-01

    The study of the adoption of information technology (IT) by individuals has taken two approaches, one emphasizing rationalistic goal-oriented behavior and the other focusing on poignant forces that influence an individual's reaction to a new IT. These approaches are not necessarily mutually exclusive. Individuals' acceptance and subsequent usage of a new IT is predicated on both. Additionally, the tendency in past studies has been to examine either the rational or the poignant factors in the context of a "resource-rich" environment-one in which there is an abundance of IT, adequate infrastructure, and a high level of acculturation to technology solutions. Consequently, there is a clear need for the examination of these factors in resource-poor environments, where assumptions on technology abundance and technology culturation do not hold. We empirically test a model that explains the intention of physicians in a resource-poor environment (epitomized by rural Ethiopia) to adopt telemedicine systems. This model integrates the rational factors driving goal-oriented behavior with the poignant/emotive factors that are an innate part of each adopter's reaction to the new technology. We use the model to expose salient contextual factors that explain the acceptance behavior of individuals toward complex information and communications technology (ICT) solutions and implications of these on the management of technology transfer initiatives in a resource-poor environment. The model is parsimonious, yet explains 28% of the variance in the intention to adopt telemedicine systems and 58% in perceived ease of use. The theoretical and practical implications of this model are discussed. Namely, Sub-Saharan African, in general, and Ethiopian culture, in particular, plays an integral role in the adoption of ICT solutions. Organizational positions and roles among physicians, clinical professionals, and superiors stand to impact the adoption of telemedicine and other healthcare

  20. Immune transfer studies in canine allogeneic marrow graft donor-recipient pairs

    SciTech Connect

    Grosse-Wilde, H.; Krumbacher, K.; Schuening, F.D.; Doxiadis, I.; Mahmoud, H.K.; Emde, C.; Schmidt-Weinmar, A.; Schaefer, U.W.

    1986-07-01

    Transfer of immunity occurring with bone marrow grafting was studied using the dog as a preclinical model. Allogeneic bone marrow transplantation (BMT) was performed between DLA-identical beagle litter-mates. The donors were immunized with tetanus toxoid (TT) or sheep red blood cells (SRBC), and their humoral response was monitored by hemagglutination. The recipients of bone marrow from TT-immunized donors showed a marked increase of antibody titer one week posttransplantation, while in the recipients of marrow from SRBC immunized donors the antibody titers were considerably lower. Within the following 60 days the antibody titers in both groups diminished gradually to pregrafting levels. Control experiments in which cell-free plasma from donors immunized with TT and SRBC respectively was transfused indicated that the initial rise of specific antibody titers after marrow grafting is likely to be due to a passive transfer of humoral immunity. A single challenge of these marrow graft recipients with the respective antigen 15-18 weeks posttransplantation led to a secondary type of humoral immune response. It could be demonstrated that transfer of memory against TT or SRBC was independent from the actual antibody titer and the time of vaccination of the donor. One dog was immunized with TT after serving as marrow donor. When the donor had shown an antibody response, a peripheral blood leukocytes (PBL) transfusion was given to his chimera. Subsequent challenge of the latter resulted in a secondary type of specific antibody response. This indicates that specific cellular-bound immunological memory can be transferred after BMT from the donor to his allogeneic bone marrow chimera by transfusion of peripheral blood leukocytes. The data may be of importance in clinical BMT to protect patients during the phase of reduced immune reactivity by transfer of memory cells.

  1. Maternal transfer of antibodies in vertebrates: trans-generational effects on offspring immunity

    PubMed Central

    Hasselquist, Dennis; Nilsson, Jan-Åke

    2008-01-01

    Maternal effects by which females provide their offspring with non-genetic factors such as hormones, nutrients and antibodies can have an important impact on offspring fitness. In vertebrates, maternal antibodies (matAb) are transferred from the mother, via the placenta, egg yolk or milk during lactation to offspring until they are 2 weeks (birds), 4–10 weeks (rodents) and 9 months (humans) old, respectively. matAb transfer can have direct effects on offspring growth rate in birds and rodents, probably by passively protecting the newborn from common pathogens before their endogenous immune system has matured. Indirect long-term effects of matAb transfer on the offspring's own immunity can be synergistic, if matAb act as antigen templates of the accumulated immunological experience of the mother and educate the newborn's immune system. However, it may also be suppressive if matAb reduce antigen presentation to the newborn resulting in antigen-specific blocking of offspring endogenous immunity. Our aim is to review the mechanisms and direct effects of matAb transfer in vertebrates with an emphasis on birds, outline a framework for research on the long-term effects of matAb on the endogenous immune system of the mature offspring and encourage ecological and evolutionary studies of matAb transfer in non-domesticated animals. PMID:18926976

  2. Tumor-derived chemokine MCP-1/CCL2 is sufficient for mediating tumor tropism of adoptively transferred T cells.

    PubMed

    Brown, Christine E; Vishwanath, Reena P; Aguilar, Brenda; Starr, Renate; Najbauer, Joseph; Aboody, Karen S; Jensen, Michael C

    2007-09-01

    To exert a therapeutic effect, adoptively transferred tumor-specific CTLs must traffic to sites of tumor burden, exit the circulation, and infiltrate the tumor microenvironment. In this study, we examine the ability of adoptively transferred human CTL to traffic to tumors with disparate chemokine secretion profiles independent of tumor Ag recognition. Using a combination of in vivo tumor tropism studies and in vitro biophotonic chemotaxis assays, we observed that cell lines derived from glioma, medulloblastoma, and renal cell carcinoma efficiently chemoattracted ex vivo-expanded primary human T cells. We compared the chemokines secreted by tumor cell lines with high chemotactic activity with those that failed to elicit T cell chemotaxis (Daudi lymphoma, 10HTB neuroblastoma, and A2058 melanoma cells) and found a correlation between tumor-derived production of MCP-1/CCL2 (> or =10 ng/ml) and T cell chemotaxis. Chemokine immunodepletion studies confirmed that tumor-derived MCP-1 elicits effector T cell chemotaxis. Moreover, MCP-1 is sufficient for in vivo T cell tumor tropism as evidenced by the selective accumulation of i.v. administered firefly luciferase-expressing T cells in intracerebral xenografts of tumor transfectants secreting MCP-1. These studies suggest that the capacity of adoptively transferred T cells to home to tumors may be, in part, dictated by the species and amounts of tumor-derived chemokines, in particular MCP-1.

  3. Microbial translocation augments the function of adoptively transferred self/tumor-specific CD8+ T cells via TLR4 signaling

    PubMed Central

    Paulos, Chrystal M.; Wrzesinski, Claudia; Kaiser,, Andrew; Hinrichs, Christian S.; Chieppa, Marcello; Cassard, Lydie; Palmer, Douglas C.; Boni, Andrea; Muranski, Pawel; Yu, Zhiya; Gattinoni, Luca; Antony, Paul A.; Rosenberg, Steven A.; Restifo, Nicholas P.

    2007-01-01

    Lymphodepletion with total body irradiation (TBI) increases the efficacy of adoptively transferred tumor-specific CD8+ T cells by depleting inhibitory lymphocytes and increasing homeostatic cytokine levels. We found that TBI augmented the function of adoptively transferred CD8+ T cells in mice genetically deficient in all lymphocytes, indicating the existence of another TBI mechanism of action. Additional investigation revealed commensal gut microflora in the mesenteric lymph nodes and elevated LPS levels in the sera of irradiated mice. These findings correlated with increased dendritic cell activation and heightened levels of systemic inflammatory cytokines. Reduction of host microflora using antibiotics, neutralization of serum LPS using polymyxin B, or removal of LPS signaling components using mice genetically deficient in CD14 and TLR4 reduced the beneficial effects of TBI on tumor regression. Conversely, administration of microbial ligand–containing serum or ultrapure LPS from irradiated animals to nonirradiated antibody-lymphodepleted mice enhanced CD8+ T cell activation and improved tumor regression. Administration of ultrapure LPS to irradiated animals further enhanced the number and function of the adoptively transferred cells, leading to long-term cure of mice with large B16F10 tumors and enhanced autoimmune vitiligo. Thus, disruption of the homeostatic balance between the host and microbes can enhance cell-based tumor immunotherapy. PMID:17657310

  4. Transfer of Immunity from Mother to Offspring Is Mediated via Egg-Yolk Protein Vitellogenin.

    PubMed

    Salmela, Heli; Amdam, Gro V; Freitak, Dalial

    2015-07-01

    Insect immune systems can recognize specific pathogens and prime offspring immunity. High specificity of immune priming can be achieved when insect females transfer immune elicitors into developing oocytes. The molecular mechanism behind this transfer has been a mystery. Here, we establish that the egg-yolk protein vitellogenin is the carrier of immune elicitors. Using the honey bee, Apis mellifera, model system, we demonstrate with microscopy and western blotting that vitellogenin binds to bacteria, both Paenibacillus larvae--the gram-positive bacterium causing American foulbrood disease--and to Escherichia coli that represents gram-negative bacteria. Next, we verify that vitellogenin binds to pathogen-associated molecular patterns; lipopolysaccharide, peptidoglycan and zymosan, using surface plasmon resonance. We document that vitellogenin is required for transport of cell-wall pieces of E. coli into eggs by imaging tissue sections. These experiments identify vitellogenin, which is distributed widely in oviparous species, as the carrier of immune-priming signals. This work reveals a molecular explanation for trans-generational immunity in insects and a previously undescribed role for vitellogenin. PMID:26230630

  5. Transfer of Immunity from Mother to Offspring Is Mediated via Egg-Yolk Protein Vitellogenin

    PubMed Central

    Salmela, Heli; Amdam, Gro V.; Freitak, Dalial

    2015-01-01

    Insect immune systems can recognize specific pathogens and prime offspring immunity. High specificity of immune priming can be achieved when insect females transfer immune elicitors into developing oocytes. The molecular mechanism behind this transfer has been a mystery. Here, we establish that the egg-yolk protein vitellogenin is the carrier of immune elicitors. Using the honey bee, Apis mellifera, model system, we demonstrate with microscopy and western blotting that vitellogenin binds to bacteria, both Paenibacillus larvae – the gram-positive bacterium causing American foulbrood disease – and to Escherichia coli that represents gram-negative bacteria. Next, we verify that vitellogenin binds to pathogen-associated molecular patterns; lipopolysaccharide, peptidoglycan and zymosan, using surface plasmon resonance. We document that vitellogenin is required for transport of cell-wall pieces of E. coli into eggs by imaging tissue sections. These experiments identify vitellogenin, which is distributed widely in oviparous species, as the carrier of immune-priming signals. This work reveals a molecular explanation for trans-generational immunity in insects and a previously undescribed role for vitellogenin. PMID:26230630

  6. Adoptive transfer of dendritic cells modulates immunogenesis and tolerogenesis in a neonatal model of murine cutaneous leishmaniasis

    PubMed Central

    Ponce, Loida V; Corado, José; Díaz, Nilka L; Tapia, Felix J

    2005-01-01

    We evaluated the adoptive transfer of DCs on Leishmania (L.) mexicana-infected neonatal BALB/c mice. DCs were isolated and purified from the spleens of the following donor groups: a) Adult BALB/c mice infected during adulthood with L. (L) mexicana; b) Adult BALB/c mice infected during neonatal life; c) Healthy neonatal BALB/c mice; d) Healthy adult BALB/c mice. A neonatal model of infection, generated after inoculation with 5 × 105 promastigotes of L. (L) mexicana, was used as the infection control group. Sixteen hours after intraperitoneal transfer of DCs (1 × 103, 1 × 105, or 1 × 106 cells/ml), neonatal recipient BALB/c mice were infected. The adoptive transfer of DCs diminished disease progression in neonatal mice. This reduction depends on the quantity and provenance of transferred DCs, since the effect was more evident with high numbers of DCs from adult mice infected during adulthood and healthy neonatal mice. Protection was significantly reduced in animals receiving DCs from healthy adult mice but it was absent in mice receiving DCs from adult mice infected during neonatal life. These results suggest that genetic susceptibility to Leishmania infection can be modified during neonatal life, and that the period of life when antigens are encountered is crucial in influencing the capacity of DCs to induce resistance or tolerance. PMID:15670331

  7. [Production of a dialysable transfer factor of cell mediated immunity by lymphoblastoid cells in continuous proliferation].

    PubMed

    Goust, J M; Viza, D; Moulias, R; Trejdosiewicz, L; Lesourd, B; Marescot, M R; Prévot, A

    1975-01-20

    Four lymphoblastoid cell lines tested in this work contain normally a dialysable moiety having by ultraviolet spectroscopy, column chromatography (Biogel P 10) and chemically the same properties than human dialysable Transfer Factor (TFd), but unable to transfer cell mediated immune response against common antigens. Two of them are able to do so after incubation with minimal amounts of TFd. Production of a molecule identical to human TFd is possible in some lymphoblastoid cell lines after induction with TFd. PMID:808340

  8. Interorganizational transfer of technology - A study of adoption of NASA innovations

    NASA Technical Reports Server (NTRS)

    Chakrabarti, A. K.; Rubenstein, A. H.

    1976-01-01

    The paper describes a study on the effects of top management support, various techno-economic factors, organizational climate, and decision-making modes on the adoption of NASA innovations. Field research consisted of interviews and questionnaires directed to sixty-five organizations. Forty-five test cases where different decisions for adoption of ideas for new products or processes were made on NASA Tech Briefs were studied in relation to the effects of various factors on the degree of success of adoption, including: (1) the degree of general connection of the technology to the firm's existing operation, (2) the specificity of the relationship between the technology and some existing and recognized problem, (3) the degree of urgency of the problem to which the technology was related, (4) maturity of technology available to implement the technology, (5) availability of personnel and financial resources to implement the technology, (6) degree of top management interest, (7) the use of confrontation in joint-decision, (8) the use of smoothing in decision-making, and (9) the use of forcing in decision-making. It was found that top managements interest was important in the product cases only, and that the success of process innovations was dependent on the quality of information and the specificity of the relationship between the technology and some recognized existing problem.

  9. Effect of regulatory cells induced by influenza virus during adoptive transfer

    SciTech Connect

    Volgarev, A.P.; Maiorova, L.P.; Smorodintsev, A.A.

    1987-06-01

    This paper examines the protective effect of humoral and cellular factors of immunity in experimental influenza infection in mice, with an analysis of the functional activity of the regulatory subpopulations of the lymphocytes, especially in the early stages of observation. The regulatory activity of the splenic lymphocytes was studied by assessing changes in the level of mitogen-induced proliferation of test cultures of lymphocytes from intact animals in the presence of lymphocytes obtained from infected mice at different times after infection. Tritium-labelled thymidine was used as the marker.

  10. Lipid Transfer Proteins As Components of the Plant Innate Immune System: Structure, Functions, and Applications

    PubMed Central

    Finkina, E. I.; Melnikova, D. N.; Bogdanov, I. V.; Ovchinnikova, T. V.

    2016-01-01

    Among a variety of molecular factors of the plant innate immune system, small proteins that transfer lipids and exhibit a broad spectrum of biological activities are of particular interest. These are lipid transfer proteins (LTPs). LTPs are interesting to researchers for three main features. The first feature is the ability of plant LTPs to bind and transfer lipids, whereby these proteins got their name and were combined into one class. The second feature is that LTPs are defense proteins that are components of plant innate immunity. The third feature is that LTPs constitute one of the most clinically important classes of plant allergens. In this review, we summarize the available data on the plant LTP structure, biological properties, diversity of functions, mechanisms of action, and practical applications, emphasizing their role in plant physiology and their significance in human life. PMID:27437139

  11. The immunologic profile of adoptively transferred lymphocytes influences stroke outcome of recipients☆

    PubMed Central

    Zierath, Dannielle; Schulze, Juliane; Kunze, Allison; Drogomiretskiy, Olga; Nhan, Derek; Jaspers, Brett; Dressel, Alexander; Becker, Kyra

    2013-01-01

    Animals that have myelin basic protein (MBP) specific lymphocytes with a Th1(+) phenotype have worse stroke outcome than those that do not. Whether these MBP specific cells contribute to worsened outcome or are merely a consequence of worse outcome is unclear. In these experiments, lymphocytes were obtained from donor animals one month after stroke and transferred to naïve recipient animals at the time of cerebral ischemia. The MBP specific phenotype of donor cells was determined prior to transfer. Animals that received either MBP specific Th1(+) or Th17(+) cells experienced worse neurological outcome, and the degree of impairment correlated with the robustness of MBP specific Th1(+) and Th17(+) responses. These data demonstrate that the immunologic phenotype of antigen specific lymphocytes influences stroke outcome. PMID:23948692

  12. Charge transfer on the metallic atom-pair bond, and the crystal structures adopted by intermetallic compounds.

    PubMed

    Rajasekharan, T; Seshubai, V

    2012-01-01

    It has been argued in our recent papers that the heat of formation of intermetallic compounds is mostly concentrated in the nearest neighbor unlike atom-pair bonds, and that the positive term in Miedema's equation is associated with charge transfer on the bond to maintain electroneutrality. In this paper, taking examples of some well populated crystal-structure types such as MgCu(2), AsNa(3), AuCu(3), MoSi(2) and SiCr(3) types, the effect of such charge transfer on the crystal structures adopted by intermetallic compounds is examined. It is shown that the correlation between the observed size changes of atoms on alloying and their electronegativity differences is supportive of the idea of charge transfer between atoms. It is argued that the electronegativity and valence differences need to be of the required magnitude and direction to alter, through charge transfer, the elemental radius ratios R(A)/R(B) to the internal radius ratios r(A)/r(B) allowed by the structure types. Since the size change of atoms on alloying is highly correlated to how different R(A)/R(B) is from the ideal radius ratio for a structure type, the lattice parameters of intermetallic compounds can be predicted with excellent accuracy knowing R(A)/R(B). A practical application of the approach developed in our recent papers to superalloy design is presented. PMID:22186292

  13. Adoptive transfer of chimeric antigen receptor re-directed cytolytic T lymphocyte clones in patients with neuroblastoma.

    PubMed

    Park, Julie R; Digiusto, David L; Slovak, Marilyn; Wright, Christine; Naranjo, Araceli; Wagner, Jamie; Meechoovet, Hunsar B; Bautista, Cherrilyn; Chang, Wen-Chung; Ostberg, Julie R; Jensen, Michael C

    2007-04-01

    Metastatic neuroblastoma is a poor-prognosis malignancy arising during childhood that overexpresses the L1-cell adhesion molecule (CD171). We have previously described a tumor L1-cell adhesion molecule-specific, single chain antibody-derived, chimeric antigen receptor designated CE7R for re-directing the antigen-specific effector functioning of cytolytic T lymphocytes. Here, we report on the feasibility of isolating, and the safety of infusing, autologous CD8(+) cytolytic T lymphocyte clones co-expressing CE7R and the selection-suicide expression enzyme HyTK in children with recurrent/refractory neuroblastoma. The cytolytic T lymphocyte products were derived from peripheral blood mononuclear cells that were subjected to polyclonal activation, plasmid vector electrotransfer, limiting dilution hygromycin selection, and expansion to numbers sufficient for adoptive transfer. In total, 12 infusions (nine at 10(8) cells/m(2), three at 10(9) cells/m(2)) were administered to six patients. No overt toxicities to tissues known to express L1-cell adhesion molecule (e.g., central nervous system, adrenal medulla, and sympathetic ganglia) were observed. The persistence of cytolytic T lymphocyte clones in the circulation, measured by vector-specific quantitative polymerase chain reaction, was short (1-7 days) in patients with bulky disease, but significantly longer (42 days) in a patient with a limited disease burden. This first-in-humans pilot study sets the stage for clinical trials employing adoptive transfer in the context of minimal residual disease.

  14. Adoptive transfer of autologous, HER2-specific, cytotoxic T lymphocytes for the treatment of HER2-overexpressing breast cancer.

    PubMed

    Bernhard, Helga; Neudorfer, Julia; Gebhard, Kerstin; Conrad, Heinke; Hermann, Christine; Nährig, Jörg; Fend, Falko; Weber, Wolfgang; Busch, Dirk H; Peschel, Christian

    2008-02-01

    The human epidermal growth factor receptor 2 (HER2) has been targeted as a breast cancer-associated antigen by immunotherapeutical approaches based on HER2-directed monoclonal antibodies and cancer vaccines. We describe the adoptive transfer of autologous HER2-specific T-lymphocyte clones to a patient with metastatic HER2-overexpressing breast cancer. The HLA/multimer-based monitoring of the transferred T lymphocytes revealed that the T cells rapidly disappeared from the peripheral blood. The imaging studies indicated that the T cells accumulated in the bone marrow (BM) and migrated to the liver, but were unable to penetrate into the solid metastases. The disseminated tumor cells in the BM disappeared after the completion of adoptive T-cell therapy. This study suggests the therapeutic potential for HER2-specific T cells for eliminating disseminated HER2-positive tumor cells and proposes the combination of T cell-based therapies with strategies targeting the tumor stroma to improve T-cell infiltration into solid tumors. PMID:17646988

  15. Drug treatment of malaria infections can reduce levels of protection transferred to offspring via maternal immunity

    PubMed Central

    Staszewski, Vincent; Reece, Sarah E.; O'Donnell, Aidan J.; Cunningham, Emma J. A.

    2012-01-01

    Maternally transferred immunity can have a fundamental effect on the ability of offspring to deal with infection. However, levels of antibodies in adults can vary both quantitatively and qualitatively between individuals and during the course of infection. How infection dynamics and their modification by drug treatment might affect the protection transferred to offspring remains poorly understood. Using the rodent malaria parasite Plasmodium chabaudi, we demonstrate that curing dams part way through infection prior to pregnancy can alter their immune response, with major consequences for offspring health and survival. In untreated maternal infections, maternally transferred protection suppressed parasitaemia and reduced pup mortality by 75 per cent compared with pups from naïve dams. However, when dams were treated with anti-malarial drugs, pups received fewer maternal antibodies, parasitaemia was only marginally suppressed, and mortality risk was 25 per cent higher than for pups from dams with full infections. We observed the same qualitative patterns across three different host strains and two parasite genotypes. This study reveals the role that within-host infection dynamics play in the fitness consequences of maternally transferred immunity. Furthermore, it highlights a potential trade-off between the health of mothers and offspring suggesting that anti-parasite treatment may significantly affect the outcome of infection in newborns. PMID:22357264

  16. Administrative simplification: adoption of operating rules for health care electronic funds transfers (EFT) and remittance advice transactions. Interim final rule with comment period.

    PubMed

    2012-08-10

    This interim final rule with comment period implements parts of section 1104 of the Affordable Care Act which requires the adoption of operating rules for the health care electronic funds transfers (EFT) and remittance advice transaction. PMID:22888504

  17. Longitudinal confocal microscopy imaging of solid tumor destruction following adoptive T cell transfer.

    PubMed

    Schietinger, Andrea; Arina, Ainhoa; Liu, Rebecca B; Wells, Sam; Huang, Jianhua; Engels, Boris; Bindokas, Vytas; Bartkowiak, Todd; Lee, David; Herrmann, Andreas; Piston, David W; Pittet, Mikael J; Lin, P Charles; Zal, Tomasz; Schreiber, Hans

    2013-11-01

    A fluorescence-based, high-resolution imaging approach was used to visualize longitudinally the cellular events unfolding during T cell-mediated tumor destruction. The dynamic interplay of T cells, cancer cells, cancer antigen loss variants, and stromal cells-all color-coded in vivo-was analyzed in established, solid tumors that had developed behind windows implanted on the backs of mice. Events could be followed repeatedly within precisely the same tumor region-before, during and after adoptive T cell therapy-thereby enabling for the first time a longitudinal in vivo evaluation of protracted events, an analysis not possible with terminal imaging of surgically exposed tumors. T cell infiltration, stromal interactions, and vessel destruction, as well as the functional consequences thereof, including the elimination of cancer cells and cancer cell variants were studied. Minimal perivascular T cell infiltrates initiated vascular destruction inside the tumor mass eventually leading to macroscopic central tumor necrosis. Prolonged engagement of T cells with tumor antigen-crosspresenting stromal cells correlated with high IFNγ cytokine release and bystander elimination of antigen-negative cancer cells. The high-resolution, longitudinal, in vivo imaging approach described here will help to further a better mechanistic understanding of tumor eradication by T cells and other anti-cancer therapies. PMID:24482750

  18. Longitudinal confocal microscopy imaging of solid tumor destruction following adoptive T cell transfer

    PubMed Central

    Schietinger, Andrea; Arina, Ainhoa; Liu, Rebecca B; Wells, Sam; Huang, Jianhua; Engels, Boris; Bindokas, Vytas; Bartkowiak, Todd; Lee, David; Herrmann, Andreas; Piston, David W; Pittet, Mikael J; Lin, P Charles; Zal, Tomasz; Schreiber, Hans

    2013-01-01

    A fluorescence-based, high-resolution imaging approach was used to visualize longitudinally the cellular events unfolding during T cell-mediated tumor destruction. The dynamic interplay of T cells, cancer cells, cancer antigen loss variants, and stromal cells—all color-coded in vivo—was analyzed in established, solid tumors that had developed behind windows implanted on the backs of mice. Events could be followed repeatedly within precisely the same tumor region—before, during and after adoptive T cell therapy—thereby enabling for the first time a longitudinal in vivo evaluation of protracted events, an analysis not possible with terminal imaging of surgically exposed tumors. T cell infiltration, stromal interactions, and vessel destruction, as well as the functional consequences thereof, including the elimination of cancer cells and cancer cell variants were studied. Minimal perivascular T cell infiltrates initiated vascular destruction inside the tumor mass eventually leading to macroscopic central tumor necrosis. Prolonged engagement of T cells with tumor antigen-crosspresenting stromal cells correlated with high IFNγ cytokine release and bystander elimination of antigen-negative cancer cells. The high-resolution, longitudinal, in vivo imaging approach described here will help to further a better mechanistic understanding of tumor eradication by T cells and other anti-cancer therapies. PMID:24482750

  19. Sodium phenylacetate inhibits adoptive transfer of experimental allergic encephalomyelitis in SJL/J mice at multiple steps.

    PubMed

    Dasgupta, Subhajit; Zhou, You; Jana, Malabendu; Banik, Naren L; Pahan, Kalipada

    2003-04-01

    Experimental allergic encephalomyelitis (EAE) is the animal model for multiple sclerosis. The present study underlines the importance of sodium phenylacetate (NaPA), a drug approved for urea cycle disorders, in inhibiting the disease process of adoptively transferred EAE in female SJL/J mice at multiple steps. Myelin basic protein (MBP)-primed T cells alone induced the expression of NO synthase (iNOS) and the activation of NF-kappaB in mouse microglial cells through cell-cell contact. However, pretreatment of MBP-primed T cells with NaPA markedly inhibited its ability to induce microglial expression of iNOS and activation of NF-kappaB. Consistently, adoptive transfer of MBP-primed T cells, but not that of NaPA-pretreated MBP-primed T cells, induced the clinical symptoms of EAE in female SJL/J mice. Furthermore, MBP-primed T cells isolated from NaPA-treated donor mice were also less efficient than MBP-primed T cells isolated from normal donor mice in inducing iNOS in microglial cells and transferring EAE to recipient mice. Interestingly, clinical symptoms of EAE were much less in mice receiving NaPA through drinking water than those without NaPA. Similar to NaPA, sodium phenylbutyrate, a chemically synthesized precursor of NaPA, also inhibited the disease process of EAE. Histological and immunocytochemical analysis showed that NaPA inhibited EAE-induced spinal cord mononuclear cell invasion and normalized iNOS, nitrotyrosine, and p65 (the RelA subunit of NF-kappaB) expression within the spinal cord. Taken together, our results raise the possibility that NaPA or sodium phenylbutyrate taken through drinking water or milk may reduce the observed neuroinflammation and disease process in multiple sclerosis patients. PMID:12646656

  20. Resolution of murine chlamydial genital infection by the adoptive transfer of a biovar-specific, Th1 lymphocyte clone.

    PubMed

    Igietseme, J U; Ramsey, K H; Magee, D M; Williams, D M; Kincy, T J; Rank, R G

    1993-01-01

    MoPn-specific T-cell clones were isolated from a T-cell line that was capable of curing chlamydial genital infection by the Chlamydia trachomatis agent of mouse pneumonitis (MoPn) after adoptive transfer. Two clones (designated as 2.14-0 and 2.14-3) were characterized by flow cytometry techniques to be homogenous for L3T4, CD3, and alpha/beta T cell receptor (TcR) T-helper cell markers. The two clones were biovar specific, because they reacted to MoPn but not the Chlamydia psittaci agent of guinea pig inclusion conjunctivitis (GPIC) or C. trachomatis, serovar type E. Cytokine profile analysis, by a combination of bioassays, ELISA, and slot/Northern blotting for specific cytokine messenger RNAs, further revealed that cultures of antigen-stimulated clone 2.14-0 contained interleukin-2 (IL-2), tumor necrosis factor-alpha, and gamma interferon (a T helper 1 cell [Th1] profile). Clone 2.14-3 was also positive for gamma interferon, a level much lower than that of clone 2.14-0, and negative for IL-4 secretion, suggesting a Th1 profile as well. The ability of these clones to bring about the resolution of the chronic genital chlamydial infection of nude mice was tested by the adoptive transfer of 10(7) cells of each clone into the mice. By 4 weeks after cell transfer of clone 2.14-0, 81% of recipient nude mice (30 of 37) resolved the disease. In contrast, clone 2.14-3 or a control T-cell clone specific for a heterologous antigen were unable to resolve the infection in 20 recipients in each case, even after 100 days.(ABSTRACT TRUNCATED AT 250 WORDS)

  1. Adoptive transfer of MART-1 T cell receptor transgenic lymphocytes and dendritic cell vaccination in patients with metastatic melanoma

    PubMed Central

    Chodon, Thinle; Comin-Anduix, Begonya; Chmielowski, Bartosz; Koya, Richard C; Wu, Zhongqi; Auerbach, Martin; Ng, Charles; Avramis, Earl; Seja, Elizabeth; Villanueva, Arturo; McCannel, Tara A.; Ishiyama, Akira; Czernin, Johannes; Radu, Caius G.; Wang, Xiaoyan; Gjertson, David W.; Cochran, Alistair J.; Cornetta, Kenneth; Wong, Deborah J.L.; Kaplan-lefko, Paula; Hamid, Omid; Samlowski, Wolfram; Cohen, Peter A.; Daniels, Gregory A.; Mukherji, Bijay; Yang, Lili; Zack, Jerome A.; Kohn, Donald B.; Heath, James R.; Glaspy, John A.; Witte, Owen N.; Baltimore, David; Economou, James S.; Ribas, Antoni

    2014-01-01

    Purpose It has been demonstrated that large numbers of tumor-specific T cells for adoptive cell transfer (ACT) can be manufactured by retroviral genetic engineering of autologous peripheral blood lymphocytes and expanding them over several weeks. In mouse models, this therapy is optimized when administered with dendritic cell (DC) vaccination. We developed a short one-week manufacture protocol to determine the feasibility, safety and antitumor efficacy of this double cell therapy. Experimnetal Design A clinical trial (NCT00910650) adoptively transferring MART-1 T cell receptor (TCR) transgenic lymphocytes together with MART-1 peptide pulsed DC vaccination in HLA-A2.1 patients with metastatic melanoma. Autologous TCR transgenic cells were manufactured in 6 to 7 days using retroviral vector gene transfer, and re-infused with (n = 10) or without (n = 3) prior cryopreservation. Results 14 patients with metastatic melanoma were enrolled and nine out of 13 treated patients (69%) showed evidence of tumor regression. Peripheral blood reconstitution with MART-1-specific T cells peaked within two weeks of ACT indicating rapid in vivo expansion. Administration of freshly manufactured TCR transgenic T cells resulted in a higher persistence of MART-1-specific T cells in the blood as compared to cryopreserved. Evidence that DC vaccination could cause further in vivo expansion was only observed with ACT using non-cryopreserved T cells. Conclusion Double cell therapy with ACT of TCR engineered T cells with a very short ex vivo manipulation and DC vaccines is feasible and results in antitumor activity, but improvements are needed to maintain tumor responses. PMID:24634374

  2. Improving Adoptive T Cell Therapy: The Particular Role of T Cell Costimulation, Cytokines, and Post-Transfer Vaccination.

    PubMed

    Redeker, Anke; Arens, Ramon

    2016-01-01

    Adoptive cellular therapy (ACT) is a form of immunotherapy whereby antigen-specific T cells are isolated or engineered, expanded ex vivo, and transferred back to patients. Clinical benefit after ACT has been obtained in treatment of infection, various hematological malignancies, and some solid tumors; however, due to poor functionality and persistence of the transferred T cells, the efficacy of ACT in the treatment of most solid tumors is often marginal. Hence, much effort is undertaken to improve T cell function and persistence in ACT and significant progress is being made. Herein, we will review strategies to improve ACT success rates in the treatment of cancer and infection. We will deliberate on the most favorable phenotype for the tumor-specific T cells that are infused into patients and on how to obtain T cells bearing this phenotype by applying novel ex vivo culture methods. Moreover, we will discuss T cell function and persistence after transfer into patients and how these factors can be manipulated by means of providing costimulatory signals, cytokines, blocking antibodies to inhibitory molecules, and vaccination. Incorporation of these T cell stimulation strategies and combinations of the different treatment modalities are likely to improve clinical response rates further. PMID:27656185

  3. Improving Adoptive T Cell Therapy: The Particular Role of T Cell Costimulation, Cytokines, and Post-Transfer Vaccination

    PubMed Central

    Redeker, Anke; Arens, Ramon

    2016-01-01

    Adoptive cellular therapy (ACT) is a form of immunotherapy whereby antigen-specific T cells are isolated or engineered, expanded ex vivo, and transferred back to patients. Clinical benefit after ACT has been obtained in treatment of infection, various hematological malignancies, and some solid tumors; however, due to poor functionality and persistence of the transferred T cells, the efficacy of ACT in the treatment of most solid tumors is often marginal. Hence, much effort is undertaken to improve T cell function and persistence in ACT and significant progress is being made. Herein, we will review strategies to improve ACT success rates in the treatment of cancer and infection. We will deliberate on the most favorable phenotype for the tumor-specific T cells that are infused into patients and on how to obtain T cells bearing this phenotype by applying novel ex vivo culture methods. Moreover, we will discuss T cell function and persistence after transfer into patients and how these factors can be manipulated by means of providing costimulatory signals, cytokines, blocking antibodies to inhibitory molecules, and vaccination. Incorporation of these T cell stimulation strategies and combinations of the different treatment modalities are likely to improve clinical response rates further.

  4. Improving Adoptive T Cell Therapy: The Particular Role of T Cell Costimulation, Cytokines, and Post-Transfer Vaccination

    PubMed Central

    Redeker, Anke; Arens, Ramon

    2016-01-01

    Adoptive cellular therapy (ACT) is a form of immunotherapy whereby antigen-specific T cells are isolated or engineered, expanded ex vivo, and transferred back to patients. Clinical benefit after ACT has been obtained in treatment of infection, various hematological malignancies, and some solid tumors; however, due to poor functionality and persistence of the transferred T cells, the efficacy of ACT in the treatment of most solid tumors is often marginal. Hence, much effort is undertaken to improve T cell function and persistence in ACT and significant progress is being made. Herein, we will review strategies to improve ACT success rates in the treatment of cancer and infection. We will deliberate on the most favorable phenotype for the tumor-specific T cells that are infused into patients and on how to obtain T cells bearing this phenotype by applying novel ex vivo culture methods. Moreover, we will discuss T cell function and persistence after transfer into patients and how these factors can be manipulated by means of providing costimulatory signals, cytokines, blocking antibodies to inhibitory molecules, and vaccination. Incorporation of these T cell stimulation strategies and combinations of the different treatment modalities are likely to improve clinical response rates further. PMID:27656185

  5. Adoptive transfer of the generalized lymphoproliferative disease (gld) syndrome in nude beige mice.

    PubMed Central

    Froidevaux, S; Rosenblatt, N; Loor, F

    1992-01-01

    C57BL/6 nude beige mice (B6 nubg) were used as recipients for the transfer of haematopoietic cells from either B6 wild as control mice, or systemic lupus erythematous B6 mice homozygous for the recessive generalized lymphadenopathy disease (gld) locus. Both gld and wild cell grafts prolonged survival of the short-living B6 nubg recipients and restored some T-cell functions, as monitored by the presence of T-dependent Ig isotypes in the serum and responsiveness of spleen cells to a T-cell mitogen. Moreover, the [gld----nubg] chimeras but not the [wild----nubg] chimeras showed several similarities with gld control mice, particularly, a spleen and lymph node hyperplasia, elevated anti-single-stranded DNA antibody titres and a hyperglobulinaemia. This hyperglobulinaemia was however qualitatively different from the gld-type hyperglobulinaemia with an important contribution of the IgG1 isotype; the lymph node hyperplasia was also less marked than in B6 gld mice. PMID:1592442

  6. Maternal antibody transfer can lead to suppression of humoral immunity in developing zebra finches (Taeniopygia guttata).

    PubMed

    Merrill, Loren; Grindstaff, Jennifer L

    2014-01-01

    Maternally transferred antibodies have been documented in a wide range of taxa and are thought to adaptively provide protection against parasites and pathogens while the offspring immune system is developing. In most birds, transfer occurs when females deposit immunoglobulin Y into the egg yolk, and it is proportional to the amount in the female's plasma. Maternal antibodies can provide short-term passive protection as well as specific and nonspecific immunological priming, but high levels of maternal antibody can result in suppression of the offspring's humoral immune response. We injected adult female zebra finches (Taeniopygia guttata) with one of two antigens (lipopolysaccharide [LPS] or keyhole limpet hemocyanin [KLH]) or a control and then injected offspring with LPS, KLH, or a control on days 5 and 28 posthatch to examine the impact of maternally transferred antibodies on the ontogeny of the offspring's humoral immune system. We found that offspring of females exposed to KLH had elevated levels of KLH-reactive antibody over the first 17-28 days posthatch but reduced KLH-specific antibody production between days 28 and 36. We also found that offspring exposed to either LPS or KLH exhibited reduced total antibody levels, compared to offspring that received a control injection. These results indicate that high levels of maternal antibodies or antigen exposure during development can have negative repercussions on short-term antibody production and may have long-term fitness repercussions for the offspring.

  7. Fate of gamma-interferon-activated killer blood monocytes adoptively transferred into the abdominal cavity of patients with peritoneal carcinomatosis

    SciTech Connect

    Stevenson, H.C.; Keenan, A.M.; Woodhouse, C.; Ottow, R.T.; Miller, P.; Steller, E.P.; Foon, K.A.; Abrams, P.G.; Beman, J.; Larson, S.M.

    1987-11-15

    Five patients with colorectal cancer widely metastatic to peritoneal surfaces have been treated i.p. with infusions of autologous blood monocytes made cytotoxic by in vitro incubation with human gamma-interferon. The monocytes were purified by a combination of cytapheresis and counter-current centrifugal elutriation procedures; each week approximately 350 million activated monocytes were given to patients as adoptive immunotherapy by a single i.p. instillation. On the eighth cycle of treatment the trafficking of i.p. infused blood monocytes was studied in two patients by prelabeling the cells with /sup 111/In. These activated cells became distributed widely within the peritoneal cavity. Two and 5 days after infusion their position within the peritoneum had not changed. When peritoneal specimens were obtained 36 h after /sup 111/In-labeled monocyte infusion, labeled monocytes were demonstrated to be associated with the serosal surfaces by autoradiographic analysis. Scintiscanning structures outside the abdominal cavity revealed that /sup 111/In-labeled monocytes infused i.p. did not traffic to other organs during the 5 days of the study. We conclude that i.p. adoptive transfer of autologous killer blood monocytes is an effective way of delivering these cytotoxic cells to sites of tumor burden on peritoneal surfaces in these cancer patients.

  8. Near-Infrared Imaging of Adoptive Immune Cell Therapy in Breast Cancer Model Using Cell Membrane Labeling

    PubMed Central

    Youniss, Fatma M.; Sundaresan, Gobalakrishnan; Graham, Laura J.; Wang, Li; Berry, Collin R.; Dewkar, Gajanan K.; Jose, Purnima; Bear, Harry D.; Zweit, Jamal

    2014-01-01

    The overall objective of this study is to non-invasively image and assess tumor targeting and retention of directly labeled T-lymphocytes following their adoptive transfer in mice. T-lymphocytes obtained from draining lymph nodes of 4T1 (murine breast cancer cell) sensitized BALB/C mice were activated in-vitro with Bryostatin/Ionomycin for 18 hours, and were grown in the presence of Interleukin-2 for 6 days. T-lymphocytes were then directly labeled with 1,1-dioctadecyltetramethyl indotricarbocyanine Iodide (DiR), a lipophilic near infrared fluorescent dye that labels the cell membrane. Assays for viability, proliferation, and function of labeled T-lymphocytes showed that they were unaffected by DiR labeling. The DiR labeled cells were injected via tail vein in mice bearing 4T1 tumors in the flank. In some cases labeled 4T1 specific T-lymphocytes were injected a week before 4T1 tumor cell implantation. Multi-spectral in vivo fluorescence imaging was done to subtract the autofluorescence and isolate the near infrared signal carried by the T-lymphocytes. In recipient mice with established 4T1 tumors, labeled 4T1 specific T-lymphocytes showed marked tumor retention, which peaked 6 days post infusion and persisted at the tumor site for up to 3 weeks. When 4T1 tumor cells were implanted 1-week post-infusion of labeled T-lymphocytes, T-lymphocytes responded to the immunologic challenge and accumulated at the site of 4T1 cell implantation within two hours and the signal persisted for 2 more weeks. Tumor accumulation of labeled 4T1 specific T-lymphocytes was absent in mice bearing Meth A sarcoma tumors. When lysate of 4T1 specific labeled T-lymphocytes was injected into 4T1 tumor bearing mice the near infrared signal was not detected at the tumor site. In conclusion, our validated results confirm that the near infrared signal detected at the tumor site represents the DiR labeled 4T1 specific viable T-lymphocytes and their response to immunologic challenge can be imaged in

  9. The dynamic impact of hydrodynamic gene transfer on the immune system

    PubMed Central

    Wu, Yan; Ma, Shoubao; Liu, Yonghao; Lei, Lei; Hu, Bo; Liu, Haiyan

    2015-01-01

    Hydrodynamic gene transfer (HGT) has been used as an effective and convenient way to achieve gene expressions in vivo. However, its time-dependent impact on the immune system is unknown. The aim of the current study is to investigate the dynamic changes of the immune parameters after HGT. Plasmids were delivered to BALB/c mice by HGT. Each group of mice was sacrificed on day 1, 2, 3, 4 and 5 after HGT. The immune cell subsets from spleens and livers were analyzed by flow cytometry. IFN-γ, IL-6 and TNF-α in the serum were quantitated by cytometric bead array. The mice without HGT injection were used as control group on day 0. Compared to the normal mice (day 0), the T lymphocyte infiltrations in the spleen and liver were increased starting from day 1 after HGT. T cells. NK cells and myeloid cells such as dendritic cells, neutrophils and macrophages were also significantly expanded and peaked around day 2-3. Both T cells and NK cells were greatly activated. Serum levels of IFN-γ and IL-6 increased and peaked on day 1 after HGT. Most of the increased immune parameters returned to normal levels after day 4. However, the activated T cells remained at a high level, especially in the liver. In conclusion, HGT significantly increased the immune cell infiltration in the spleen and liver and activated T cells and NK cells. The immune response induced by HGT should be taken into consideration when evaluating the functions of the over-expressed genes using this strategy. PMID:26309505

  10. Prenatal passive transfer of maternal immunity in Asian elephants (Elephas maximus).

    PubMed

    Nofs, Sally A; Atmar, Robert L; Keitel, Wendy A; Hanlon, Cathleen; Stanton, Jeffrey J; Tan, Jie; Flanagan, Joseph P; Howard, Lauren; Ling, Paul D

    2013-06-15

    Asian (Elephas maximus) and African (Loxodonta africana) elephants exhibit characteristics of endotheliochorial placentation, which is common in carnivore species and is associated with modest maternal to fetal transplacental antibody transfer. However, it remains unknown whether the bulk of passive immune transfer in elephants is achieved prenatally or postnatally through ingestion of colostrum, as has been documented for horses, a species whose medical knowledgebase is often extrapolated for elephants. To address this issue, we took advantage of the fact that many zoo elephants are immunized with tetanus toxoid and/or rabies vaccines as part of their routine health care, allowing a comparison of serum antibody levels against these antigens between dams and neonates. Serum samples were collected from 3 newborn Asian elephant calves at birth (before ingestion of colostrum); 2-4 days after birth; and 2-3 months of age. The findings indicate that the newborns had anti-tetanus toxoid and anti-rabies titers that were equivalent to or higher than the titers of their dams from birth to approximately 3 months of age, suggesting that the majority of maternal-to-fetal transfer is transplacental and higher than expected based on the architecture of the Asian elephant placenta.

  11. Immune response in mice to ingested soya protein: antibody production, oral tolerance and maternal transfer.

    PubMed

    Christensen, Hanne R; Brix, Susanne; Frøkiaer, Hanne

    2004-05-01

    While allergic reactions to soya are increasingly investigated, the normal immune response to ingested soya is scarcely described. In the present study, we wanted to characterise the soya-specific immune response in healthy mice ingesting soya protein. Mice fed a soya-containing diet (F0) and mice of the first (F1) and second (F2) offspring generation bred on a soya protein-free diet were used either directly or were transferred between the soya-containing and soya protein-free diet during pregnancy or neonatal life. The mice were compared as to levels of naturally occurring specific antibodies analysed by ELISA, and to the presence of oral tolerance detected as a suppressed antibody and cell-proliferation response upon immunisation with soya protein. F0 mice generated soya-specific antibodies, while oral tolerance to the same soya proteins was also clearly induced. When F0 dams were transferred to soya protein-free feed before mating, the F1 and F2 offspring generations showed no significantly different response, indicating that soya-specific immune components were not maternally transmitted. However, the ingestion of dietary soya protein by F1 mice during late pregnancy and lactation caused a lasting antibody response in the offspring, but in this case in the absence of oral tolerance. This indicates that, under certain conditions, factors involved in spontaneous antibody production can be transmitted from mother to offspring. Understanding the immune response to soya protein ingested under healthy conditions is important in the assessment of adverse effects of soya protein and in the use of animal allergy models. The present results add to this understanding. PMID:15137924

  12. Immunization

    MedlinePlus

    ... a lot worse. Some are even life-threatening. Immunization shots, or vaccinations, are essential. They protect against things like measles, ... B, polio, tetanus, diphtheria, and pertussis (whooping cough). Immunizations are important for adults as well as children. ...

  13. Immunizations

    MedlinePlus

    ... How Can I Help a Friend Who Cuts? Immunizations KidsHealth > For Teens > Immunizations Print A A A ... That Shot? en español Las vacunas Why Are Vaccinations Important? Measles, mumps, and whooping cough may seem ...

  14. GVHD-associated, inflammasome-mediated loss of function in adoptively transferred myeloid-derived suppressor cells.

    PubMed

    Koehn, Brent H; Apostolova, Petya; Haverkamp, Jessica M; Miller, Jeffrey S; McCullar, Valarie; Tolar, Jakub; Munn, David H; Murphy, William J; Brickey, Willie June; Serody, Jonathan S; Gabrilovich, Dmitry I; Bronte, Vincenzo; Murray, Peter J; Ting, Jenny P-Y; Zeiser, Robert; Blazar, Bruce R

    2015-09-24

    Myeloid-derived suppressor cells (MDSCs) are a naturally occurring immune regulatory population associated with inhibition of ongoing inflammatory responses. In vitro generation of MDSCs from bone marrow has been shown to enhance survival in an acute model of lethal graft-versus-host disease (GVHD). However, donor MDSC infusion only partially ameliorates GVHD lethality. In order to improve the potential therapeutic benefit and ultimately survival outcomes, we set out to investigate the fate of MDSCs after transfer in the setting of acute GVHD (aGVHD). MDSCs transferred to lethally irradiated recipients of allogeneic donor hematopoietic grafts are exposed to an intense inflammatory environment associated with aGVHD, which we now show directly undermines their suppressive capacity. Under a conditioning regimen and GVHD inflammatory settings, MDSCs rapidly lose suppressor function and their potential to inhibit GVHD lethality, which is associated with their induced conversion toward a mature inflammasome-activated state. We find even brief in vitro exposure to inflammasome-activating mediators negates the suppressive potential of cultured murine and human-derived MDSCs. Consistent with a role for the inflammasome, donor MDSCs deficient in the adaptor ASC (apoptosis-associated speck-like protein containing a CARD), which assembles inflammasome complexes, conferred improved survival of mice developing GVHD compared with wild-type donor MDSCs. These data suggest the use of MDSCs as a therapeutic approach for preventing GVHD and other systemic inflammatory conditions will be more effective when combined with approaches limiting in vivo MDSC inflammasome activation, empowering MDSCs to maintain their suppressive potential.

  15. GVHD-associated, inflammasome-mediated loss of function in adoptively transferred myeloid-derived suppressor cells

    PubMed Central

    Koehn, Brent H.; Apostolova, Petya; Haverkamp, Jessica M.; Miller, Jeffrey S.; McCullar, Valarie; Tolar, Jakub; Munn, David H.; Murphy, William J.; Brickey, Willie June; Serody, Jonathan S.; Gabrilovich, Dmitry I.; Bronte, Vincenzo; Murray, Peter J.; Ting, Jenny P.-Y.; Zeiser, Robert

    2015-01-01

    Myeloid-derived suppressor cells (MDSCs) are a naturally occurring immune regulatory population associated with inhibition of ongoing inflammatory responses. In vitro generation of MDSCs from bone marrow has been shown to enhance survival in an acute model of lethal graft-versus-host disease (GVHD). However, donor MDSC infusion only partially ameliorates GVHD lethality. In order to improve the potential therapeutic benefit and ultimately survival outcomes, we set out to investigate the fate of MDSCs after transfer in the setting of acute GVHD (aGVHD). MDSCs transferred to lethally irradiated recipients of allogeneic donor hematopoietic grafts are exposed to an intense inflammatory environment associated with aGVHD, which we now show directly undermines their suppressive capacity. Under a conditioning regimen and GVHD inflammatory settings, MDSCs rapidly lose suppressor function and their potential to inhibit GVHD lethality, which is associated with their induced conversion toward a mature inflammasome-activated state. We find even brief in vitro exposure to inflammasome-activating mediators negates the suppressive potential of cultured murine and human-derived MDSCs. Consistent with a role for the inflammasome, donor MDSCs deficient in the adaptor ASC (apoptosis-associated speck-like protein containing a CARD), which assembles inflammasome complexes, conferred improved survival of mice developing GVHD compared with wild-type donor MDSCs. These data suggest the use of MDSCs as a therapeutic approach for preventing GVHD and other systemic inflammatory conditions will be more effective when combined with approaches limiting in vivo MDSC inflammasome activation, empowering MDSCs to maintain their suppressive potential. PMID:26265697

  16. Passive transfer of naturally acquired specific immunity against West Nile Virus to foals in a semi-feral pony herd.

    PubMed

    Wilkins, Pamela A; Glaser, Amy L; McDonnell, Sue M

    2006-01-01

    Horses naturally exposed to West Nile Virus (WNV) or vaccinated against WNV develop humoral immunity thought to be protective against development of clinical disease in exposed or infected animals. No reports evaluate the efficacy of passive transfer of naturally acquired specific WNV humoral immunity from dam to foal. The purpose of this study was to investigate passive transfer of naturally acquired immunity to WNV to foals born in a herd of semi-feral ponies, not vaccinated against WNV, in an endemic area, with many dams having seroconverted because of natural exposure. Microwell serum neutralization titers against WNV were determined in all mares and foals. Serum IgG concentration was determined in foals by serial radial immunodiffusion. Differences in IgG concentration between seropositive and seronegative foals were examined by means of the Mann-Whitney U-test. Linear regression was used to evaluate the association between mare and foal titers. Seventeen mare-foal pairs were studied; 1 foal had inadequate IgG concentration. IgG concentration was not different between seronegative and seropositive foals (P = .24). Mare and foal titers were significantly correlated in foals with adequate passive transfer of immunity (Spearman's rho = .84; P < .001); >90% of the foal's titer was explained by the mare's titer (R2 = 0.91; P < .001). Passive transfer of specific immunity to WNV is present in pony foals with adequate passive transfer of immunity born to seroconverted mares.

  17. Adoptive Transfer of Ex Vivo HO-1 Modified Bone Marrow–derived Macrophages Prevents Liver Ischemia and Reperfusion Injury

    PubMed Central

    Ke, Bibo; Shen, Xiu-Da; Gao, Feng; Ji, Haofeng; Qiao, Bo; Zhai, Yuan; Farmer, Douglas G; Busuttil, Ronald W; Kupiec-Weglinski, Jerzy W

    2009-01-01

    Macrophages play a critical role in the pathophysiology of liver ischemia and reperfusion (IR) injury (IRI). However, macrophages that overexpress antioxidant heme oxygenase-1 (HO-1) may exert profound anti-inflammatory functions. This study explores the cytoprotective effects and mechanisms of ex vivo modified HO-1-expressing bone marrow–derived macrophages (BMDMs) in well-defined mouse model of liver warm ischemia followed by reperfusion. Adoptive transfer of Ad-HO-1-transduced macrophages prevented IR-induced hepatocellular damage, as evidenced by depressed serum glutamic-oxaloacetic transaminase (sGOT) levels and preserved liver histology (Suzuki scores), compared to Ad-β-gal controls. This beneficial effect was reversed following concomitant treatment with HO-1 siRNA. Ad-HO-1-transfected macrophages significantly decreased local neutrophil accumulation, TNF-α/IL-1β, IFN-γ/E-selectin, and IP-10/MCP-1 expression, caspase-3 activity, and the frequency of apoptotic cells, as compared with controls. Unlike in controls, Ad-HO-1-transfected macrophages markedly increased hepatic expression of antiapoptotic Bcl-2/Bcl-xl and depressed caspase-3 activity. These results establish the precedent for a novel investigative tool and provide the rationale for a clinically attractive new strategy in which native macrophages can be transfected ex vivo with cytoprotective HO-1 and then infused, if needed, to prospective recipients exposed to hepatic IR–mediated local inflammation, such as during liver transplantation, resection, or trauma. PMID:20029397

  18. An HSV-2 based oncolytic virus can function as an attractant to guide migration of adoptively transferred T cells to tumor sites

    PubMed Central

    Tao, Lihua; Zhang, Xiaoliu

    2015-01-01

    Adoptive T-cell therapy has shown promises for cancer treatment. However, for treating solid tumors, there is a need for improving the ability of the adoptively transferred T cells to home to tumor sites. We explored the possibility of using an oncolytic virus derived from HSV-2, which can actively pull T effector cells to the site of infection, as a local attractant for migration of adoptively transferred T cells. Our data show that intratumoral administration of this virus can indeed attract active migration of the adoptively transferred T cells to the treated tumor. Moreover, once attracted to the tumor site by the virus, T cells persisted in there significantly longer than in mock-treated tumor. Chemokine profiling identified significant elevation of CXCL9 and CXCL10, as well as several other chemokines belonging to the inflammatory chemokine family in the virus-treated tumors. These chemokines initially guided the T-cell migration to and then maintained their persistence in the tumor site, leading to a significantly enhanced therapeutic effect. Our data suggests that this virotherapy may be combined with adoptive T-cell therapy to potentiate its therapeutic effect against solid tumors that are otherwise difficult to manage with the treatment alone. PMID:25460506

  19. Sex-specific effects of maternal immunization on yolk antibody transfer and offspring performance in zebra finches

    PubMed Central

    Martyka, Rafał; Rutkowska, Joanna; Cichoń, Mariusz

    2011-01-01

    Trans-generational antibody transfer constitutes an important mechanism by which mothers may enhance offspring resistance to pathogens. Thus, differential antibody deposition may potentially allow a female to differentiate offspring performance. Here, we examined whether maternal immunization with sheep red blood cells (SRBC) prior to egg laying affects sex-specific yolk antibody transfer and sex-specific offspring performance in zebra finches (Taeniopygia guttata). We showed that immunized mothers deposit anti-SRBC antibodies into the eggs depending on embryo sex and laying order, and that maternal exposure to SRBC positively affects the body size of female, but not male offspring. This is the first study reporting sex-specific consequences of maternal immunization on offspring performance, and suggests that antibody transfer may constitute an adaptive mechanism of maternal favouritism. PMID:20667842

  20. Perforin gene transfer into hematopoietic stem cells improves immune dysregulation in murine models of perforin deficiency.

    PubMed

    Carmo, Marlene; Risma, Kimberly A; Arumugam, Paritha; Tiwari, Swati; Hontz, Adrianne E; Montiel-Equihua, Claudia A; Alonso-Ferrero, Maria E; Blundell, Michael P; Schambach, Axel; Baum, Christopher; Malik, Punam; Thrasher, Adrian J; Jordan, Michael B; Gaspar, H Bobby

    2015-04-01

    Defects in perforin lead to the failure of T and NK cell cytotoxicity, hypercytokinemia, and the immune dysregulatory condition known as familial hemophagocytic lymphohistiocytosis (FHL). The only curative treatment is allogeneic hematopoietic stem cell transplantation which carries substantial risks. We used lentiviral vectors (LV) expressing the human perforin gene, under the transcriptional control of the ubiquitous phosphoglycerate kinase promoter or a lineage-specific perforin promoter, to correct the defect in different murine models. Following LV-mediated gene transfer into progenitor cells from perforin-deficient mice, we observed perforin expression in mature T and NK cells, and there was no evidence of progenitor cell toxicity when transplanted into irradiated recipients. The resulting perforin-reconstituted NK cells showed partial recovery of cytotoxicity, and we observed full recovery of cytotoxicity in polyclonal CD8(+) T cells. Furthermore, reconstituted T cells with defined antigen specificity displayed normal cytotoxic function against peptide-loaded targets. Reconstituted CD8(+) lymphoblasts had reduced interferon-γ secretion following stimulation in vitro, suggesting restoration of normal immune regulation. Finally, upon viral challenge, mice with >30% engraftment of gene-modified cells exhibited reduction of cytokine hypersecretion and cytopenias. This study demonstrates the potential of hematopoietic stem cell gene therapy as a curative treatment for perforin-deficient FHL.

  1. Perforin gene transfer into hematopoietic stem cells improves immune dysregulation in murine models of perforin deficiency.

    PubMed

    Carmo, Marlene; Risma, Kimberly A; Arumugam, Paritha; Tiwari, Swati; Hontz, Adrianne E; Montiel-Equihua, Claudia A; Alonso-Ferrero, Maria E; Blundell, Michael P; Schambach, Axel; Baum, Christopher; Malik, Punam; Thrasher, Adrian J; Jordan, Michael B; Gaspar, H Bobby

    2015-04-01

    Defects in perforin lead to the failure of T and NK cell cytotoxicity, hypercytokinemia, and the immune dysregulatory condition known as familial hemophagocytic lymphohistiocytosis (FHL). The only curative treatment is allogeneic hematopoietic stem cell transplantation which carries substantial risks. We used lentiviral vectors (LV) expressing the human perforin gene, under the transcriptional control of the ubiquitous phosphoglycerate kinase promoter or a lineage-specific perforin promoter, to correct the defect in different murine models. Following LV-mediated gene transfer into progenitor cells from perforin-deficient mice, we observed perforin expression in mature T and NK cells, and there was no evidence of progenitor cell toxicity when transplanted into irradiated recipients. The resulting perforin-reconstituted NK cells showed partial recovery of cytotoxicity, and we observed full recovery of cytotoxicity in polyclonal CD8(+) T cells. Furthermore, reconstituted T cells with defined antigen specificity displayed normal cytotoxic function against peptide-loaded targets. Reconstituted CD8(+) lymphoblasts had reduced interferon-γ secretion following stimulation in vitro, suggesting restoration of normal immune regulation. Finally, upon viral challenge, mice with >30% engraftment of gene-modified cells exhibited reduction of cytokine hypersecretion and cytopenias. This study demonstrates the potential of hematopoietic stem cell gene therapy as a curative treatment for perforin-deficient FHL. PMID:25523759

  2. Using a Scripted Data Entry Process to Transfer Legacy Immunization Data While Transitioning Between Electronic Medical Record Systems

    PubMed Central

    Michel, J.; Hsiao, A.; Fenick, A.

    2014-01-01

    Summary Background Transitioning between Electronic Medical Records (EMR) can result in patient data being stranded in legacy systems with subsequent failure to provide appropriate patient care. Manual chart abstraction is labor intensive, error-prone, and difficult to institute for immunizations on a systems level in a timely fashion. Objectives We sought to transfer immunization data from two of our health system’s soon to be replaced EMRs to the future EMR using a single process instead of separate interfaces for each facility. Methods We used scripted data entry, a process where a computer automates manual data entry, to insert data into the future EMR. Using the Center for Disease Control’s CVX immunization codes we developed a bridge between immunization identifiers within our system’s EMRs. We performed a two-step process evaluation of the data transfer using automated data comparison and manual chart review. Results We completed the data migration from two facilities in 16.8 hours with no data loss or corruption. We successfully populated the future EMR with 99.16% of our legacy immunization data – 500,906 records – just prior to our EMR transition date. A subset of immunizations, first recognized during clinical care, had not originally been extracted from the legacy systems. Once identified, this data – 1,695 records – was migrated using the same process with minimal additional effort. Conclusions Scripted data entry for immunizations is more accurate than published estimates for manual data entry and we completed our data transfer in 1.2% of the total time we predicted for manual data entry. Performing this process before EMR conversion helped identify obstacles to data migration. Drawing upon this work, we will reuse this process for other healthcare facilities in our health system as they transition to the future EMR. PMID:24734139

  3. Enhanced anti-tumor activity induced by adoptive T cell transfer and the adjunctive use of the HDAC Inhibitor LAQ824

    PubMed Central

    Vo, Dan D.; Prins, Robert M.; Begley, Jonathan L.; Donahue, Timothy R.; Morris, Lilah F.; Bruhn, Kevin W.; de la Rocha, Pilar; Yang, Meng-Yin; Mok, Stephen; Garban, Hermes J.; Craft, Noah; Economou, James S.; Marincola, Francesco M.; Wang, Ena; Ribas, Antoni

    2009-01-01

    Tumors grow in the presence of antigen-specific T cells, suggesting the existence of intrinsic cancer cell escape mechanisms. We hypothesized that a histone deacetylase (HDAC) inhibitor could sensitize tumor cells to immunotherapy because this class of agents has been reported to increase tumor antigen expression and shift gene expression to a pro-apoptotic milieu in cancer cells. To test this question, we treated B16 murine melanoma with the combination of the HDAC inhibitor LAQ824 together with the adoptive transfer (AT) of gp100 melanoma antigen-specific pmel-1 T cells. The combined therapy significantly improved antitumor activity through several mechanisms: 1) increase in MHC and tumor-associated antigen (TAA) expression by tumor cells; 2) decrease in competing endogenous lymphocytes in recipient mice, resulting in a proliferative advantage for the adoptively transferred cells; and 3) improvement in the functional activity of the adoptively transferred lymphocytes. We confirmed the beneficial effects of this HDAC inhibitor as sensitizer to immunotherapy in a different model of prophylactic prime-boost vaccination with the melanoma antigen tyrosinase-related protein-2 (TRP2), which also demonstrated a significant improvement in antitumor activity against B16 melanoma. In conclusion, the HDAC inhibitor LAQ824 significantly enhances tumor immunotherapy through effects on target tumor cells as well as improving the antitumor activity of tumor antigen-specific lymphocytes. PMID:19861533

  4. Identification of a Novel Immunodominant HLA-B*07: 02-restricted Adenoviral Peptide Epitope and Its Potential in Adoptive Transfer Immunotherapy.

    PubMed

    Günther, Patrick S; Peper, Janet K; Faist, Benjamin; Kayser, Simone; Hartl, Lena; Feuchtinger, Tobias; Jahn, Gerhard; Neuenhahn, Michael; Busch, Dirk H; Stevanović, Stefan; Dennehy, Kevin M

    2015-09-01

    Adenovirus infections of immunocompromised patients, particularly following allogeneic hematopoietic stem cell transplantation, are associated with morbidity and mortality. Immunotherapy by adoptive transfer of hexon-specific and penton-specific T cells has been successfully applied, but many approaches are impeded by the low number of HLA class I-restricted adenoviral peptide epitopes described to date. We use a novel method to identify naturally presented adenoviral peptide epitopes from infected human cells, ectopically expressing defined HLA, using peptide elution and liquid chromatography-mass spectrometry analysis. We show that the previously described HLA-A*01:01-restricted peptide epitope LTDLGQNLLY from hexon protein is naturally presented, and demonstrate the functionality of LTDLGQNLLY-specific T cells. We further identify a novel immunodominant HLA-B*07:02-restricted peptide epitope VPATGRTLVL from protein 13.6 K, and demonstrate the high proliferative, cytotoxic, and IFN-γ-producing capacity of peptide-specific T cells. Lastly, LTDLGQNLLY-specific T cells can be detected ex vivo following adoptive transfer therapy, and LTDLGQNLLY-specific and VPATGRTLVL-specific T cells have memory phenotypes ex vivo. Given their proliferative and cytotoxic capacity, such epitope-specific T cells are promising candidates for adoptive T-cell transfer therapy of adenovirus infection.

  5. Immunization.

    ERIC Educational Resources Information Center

    Guerin, Nicole; And Others

    1986-01-01

    Contents of this double journal issue concern immunization and primary health care of children. The issue decribes vaccine storage and sterilization techniques, giving particular emphasis to the role of the cold chain, i.e., the maintenance of a specific temperature range to assure potency of vaccines as they are moved from a national storage…

  6. CXCL10-induced migration of adoptively transferred human natural killer cells toward solid tumors causes regression of tumor growth in vivo.

    PubMed

    Wennerberg, Erik; Kremer, Veronika; Childs, Richard; Lundqvist, Andreas

    2015-02-01

    Adoptive infusion of natural killer (NK) cells is being increasingly explored as a therapy in patients with cancer, although clinical responses are thus far limited to patients with hematological malignancies. Inadequate homing of infused NK cells to the tumor site represents a key factor that may explain the poor anti-tumor effect of NK cell therapy against solid tumors. One of the major players in the regulation of lymphocyte chemotaxis is the chemokine receptor chemokine (C-X-C motif) receptor 3 (CXCR3) which is expressed on activated NK cells and induces NK cell migration toward gradients of the chemokine (C-X-C motif) ligand (CXCL9, 10 and 11). Here, we show that ex vivo expansion of human NK cells results in a tenfold increased expression of the CXCR3 receptor compared with resting NK cells (p = 0.04). Consequently, these NK cells displayed an improved migratory capacity toward solid tumors, which was dependent on tumor-derived CXCL10. In xenograft models, adoptively transferred NK cells showed increased migration toward CXCL10-transfected melanoma tumors compared with CXCL10-negative wild-type tumors, resulting in significantly reduced tumor burden and increased survival (median survival 41 vs. 32 days, p = 0.03). Furthermore, administration of interferon-gamma locally in the tumor stimulated the production of CXCL10 in subcutaneous melanoma tumors resulting in increased infiltration of adoptively transferred CXCR3-positive expanded NK cells. Our findings demonstrate the importance of CXCL10-induced chemoattraction in the anti-tumor response of adoptively transferred expanded NK cells against solid melanoma tumors.

  7. Increased plasma-immune cytokines throughout the high-dose melphalan-induced lymphodepletion in patients with multiple myeloma: a window for adoptive immunotherapy.

    PubMed

    Condomines, Maud; Veyrune, Jean-Luc; Larroque, Marion; Quittet, Philippe; Latry, Pascal; Lugagne, Cécile; Hertogh, Catherine; Kanouni, Tarik; Rossi, Jean-François; Klein, Bernard

    2010-01-15

    High-dose melphalan (HDM) followed by autologous stem cell transplantation (ASCT) is a standard treatment for patients with multiple myeloma. However, lymphocyte reconstitution is impaired after HDM. Recent work has suggested that the lymphopenia period occurring after various immunosuppressive or chemotherapy treatments may provide an interesting opportunity for adoptive antitumor immunotherapy. The objective of this study was to determine an immunotherapy window after HDM and ASCT, evaluating T cell lymphopenia, and measuring circulating immune cytokine concentrations in patients with multiple myeloma. The counts of T cell subpopulations reached a nadir at day 8 post-ASCT (day 10 post-HDM) and recovered by day 30. IL-6, IL-7, and IL-15 plasma levels increased on a median day 8 post-ASCT, respectively, 35-fold, 8-fold, and 10-fold compared with pre-HDM levels (p < or = 0.05). The increases in IL-7 and IL-15 levels were inversely correlated to the absolute lymphocyte count, unlike monocyte or myeloid counts. Furthermore, we have shown that CD3 T cells present in the ASC graft are activated, die rapidly when they are cultured without cytokine in vitro, and that addition of IL-7 or IL-15 could induce their survival and proliferation. In conclusion, the early lymphodepletion period, occurring 4-11 d post-HDM and ASCT, is associated with an increase of circulating immune cytokines and could be an optimal window to enhance the survival and proliferation of polyclonal T cells present in the ASC autograft and also of specific antimyeloma T cells previously expanded in vitro.

  8. Income transfer policies and the impacts on the immunization of children: the Bolsa Família Program.

    PubMed

    Andrade, Mônica Viegas; Chein, Flávia; Souza, Laetícia Rodrigues de; Puig-Junoy, Jaume

    2012-07-01

    This paper investigates the impact of the Bolsa Família Program on the immunization of children from 0 to 6 years of age in Brazil and its regions. The Bolsa Família program is a conditional cash transfer program. One of its conditionalities is the compliance of children with the immunization schedule ordered by the Ministry of Health. The evaluation was performed using the Propensity Score Matching technique. We used data from a survey conducted in 2005 evaluating the program - Pesquisa de Avaliação de Impacto do Programa Bolsa Família. The main findings suggest that the Bolsa Família Program does not affect the immunization status of children.

  9. Whole-body irradiation increases the magnitude and persistence of adoptively transferred T cells associated with tumor regression in a mouse model of prostate cancer

    PubMed Central

    Ward-Kavanagh, Lindsay K.; Zhu, Junjia; Cooper, Timothy K.; Schell, Todd D.

    2014-01-01

    Adoptive immunotherapy has demonstrated efficacy in a subset of clinical and preclinical studies, but the T cells used for therapy often are rendered rapidly non-functional in tumor-bearing hosts. Recent evidence indicates that prostate cancer can be susceptible to immunotherapy, but most studies using autochthonous tumor models demonstrate only short-lived T-cell responses in the tolerogenic prostate microenvironment. Here, we assessed the efficacy of sublethal whole-body irradiation (WBI) to enhance the magnitude and duration of adoptively transferred CD8+ T cells in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model. We demonstrate that WBI promoted high-level accumulation of granzyme B (GzB)-expressing donor T cells both in lymphoid organs and in the prostate of TRAMP mice. Donor T cells remained responsive to vaccination in irradiated recipients, but a single round of WBI-enhanced adoptive immunotherapy failed to impact significantly the existing disease. Addition of a second round of immunotherapy promoted regression of established disease in half of the treated mice, with no progressions observed. Regression was associated with long-term persistence of effector/memory phenotype CD8+ donor cells. Administration of the second round of adoptive immunotherapy led to reacquisition of GzB expression by persistent T cells from the first transfer. These results indicate that WBI conditioning amplifies tumor-specific T cells in the TRAMP prostate and lymphoid tissue, and suggest that the initial treatment alters the tolerogenic microenvironment to increase antitumor activity by a second wave of donor cells. PMID:24801834

  10. Role of memory T cell subsets for adoptive immunotherapy.

    PubMed

    Busch, Dirk H; Fräßle, Simon P; Sommermeyer, Daniel; Buchholz, Veit R; Riddell, Stanley R

    2016-02-01

    Adoptive transfer of primary (unmodified) or genetically engineered antigen-specific T cells has demonstrated astonishing clinical results in the treatment of infections and some malignancies. Besides the definition of optimal targets and antigen receptors, the differentiation status of transferred T cells is emerging as a crucial parameter for generating cell products with optimal efficacy and safety profiles. Long-living memory T cells subdivide into phenotypically as well as functionally different subsets (e.g. central memory, effector memory, tissue-resident memory T cells). This diversification process is crucial for effective immune protection, with probably distinct dependencies on the presence of individual subsets dependent on the disease to which the immune response is directed as well as its organ location. Adoptive T cell therapy intends to therapeutically transfer defined T cell immunity into patients. Efficacy of this approach often requires long-term maintenance of transferred cells, which depends on the presence and persistence of memory T cells. However, engraftment and survival of highly differentiated memory T cell subsets upon adoptive transfer is still difficult to achieve. Therefore, the recent observation that a distinct subset of weakly differentiated memory T cells shows all characteristics of adult tissue stem cells and can reconstitute all types of effector and memory T cell subsets, became highly relevant. We here review our current understanding of memory subset formation and T cell subset purification, and its implications for adoptive immunotherapy.

  11. Effect of dam parity on litter performance, transfer of passive immunity, and progeny microbial ecology.

    PubMed

    Carney-Hinkle, E E; Tran, H; Bundy, J W; Moreno, R; Miller, P S; Burkey, T E

    2013-06-01

    (P < 0.03) Shannon's diversity index compared with P4 progeny on d 7. Litter performance, passive transfer of immunity, and progeny microbial ecology were affected by dam parity.

  12. Trans-Epithelial Immune Cell Transfer during Suckling Modulates Delayed-Type Hypersensitivity in Recipients as a Function of Gender

    PubMed Central

    Ma, Lisa J.; Walter, Barbara; DeGuzman, Ariel; Muller, H. Konrad; Walker, Ameae M.

    2008-01-01

    Introduction Breast feeding has long term effects on the developing immune system which outlive passive immunization of the neonate. We have investigated the transfer of milk immune cells and examined the result of transfer once the recipients were adult. Methods Non-transgenic mouse pups were foster-nursed by green fluorescent protein (GFP) transgenic dams for 3 weeks and the fate of GFP+ cells was followed by FACS analysis, immunohistochemistry and RT-PCR for GFP and appropriate immune cell markers. Pups suckled by non-transgenic dams served as controls. Results Despite a preponderance of B cells and macrophages in the stomach contents of the pups, most cells undergoing trans-epithelial migration derived from the 3–4% of milk cells positive for T lymphocyte markers. These cells homed to the spleen and thymus, with maximal accumulation at 3–4 weeks. By sensitizing dams with an antigen which elicits a T cell-mediated delayed-type-hypersensitivity (DTH) response, we determined that nursing by a sensitized dam (compared to a non-sensitized dam) amplified a subsequent DTH response in females and yet suppressed one in males. Discussion These results suggest that clinical evaluation weighing the pros and cons of nursing male versus female children by mothers with genetically-linked hypersensitivity diseases, such as celiac disease and eczema, or those in regions of the world with endemic DTH-eliciting diseases, such as tuberculosis, may be warranted. PMID:18958163

  13. Active immunizations with peptide-DC vaccines and passive transfer with antibodies protect neutropenic mice against disseminated candidiasis.

    PubMed

    Xin, Hong

    2016-01-01

    We previously report that peptide-pulsed dendritic cell (DC) vaccination, which targeting two peptides (Fba and Met6) expressed on the cell surface of Candida albicans, can induce high degree of protection against disseminated candidiasis in immunocompetent mice. Passive transfer of immune sera from the peptide immunized mice or peptide-related monoclonal antibodies demonstrated that protection was medicated by peptide-specific antibodies. In this study the efficacy of active and passive immunization against disseminated candidiasis was tested in mice with cyclophosphamide-induced neutropenia. Peptide-DC vaccines were given to mice prior to induction of neutropenia. We show active immunization with either Fba or Met6 peptide-DC vaccine significantly improved the survival and reduced the fungal burden of disseminated candidiasis in those immunocompromised mice. Importantly, we show that administration of two protective monoclonal antibodies also protect neutropenic mice against the disease, implying possibility of developing a successful passive immunotherapy strategy to treat the disease and protect against disseminated candidiasis. The results of this study are crucial as they address the fundamental questions as to whether the synthetic peptide vaccine induced immunity protects the host during a neutropenic episode. We anticipate that this peptide-vaccine study will serve as the foundation of future investigations into new peptide vaccines comprised of cell surface peptides from other medically important Candida species, as well as other fungi.

  14. Adoptive transfer of cytotoxic T lymphocytes induced by CD86-transfected tumor cells suppresses multi-organ metastases of C1300 neuroblastoma in mice.

    PubMed

    Enomoto, A; Kato, K; Yagita, H; Okumura, K

    1997-06-01

    In this study, we examined the therapeutic antitumor effect of cytotoxic T lymphocytes (CTL) generated against CD86-transfected mouse neuroblastoma C1300. We first generated the transfectant, CD86 + C1300, expressing a high level of mouse CD86 on the cell surface. While CD86 + C1300 cells were rejected in syngeneic A/J mice when inoculated subcutaneously, neither vaccination nor any therapeutic antitumor effect was obtained, implying that C1300 may be a poorly immunogenic tumor. However, in vitro stimulation of splenocytes from either C1300-bearing or CD86 + C1300-rejecting mice with CD86 + C1300 cells resulted in remarkable CTL activity against C1300 cells. The CTL activity induced by CD86 + C1300 was mediated by T cell receptor/CD3 and CD8 and was further enhanced by the addition of interleukin-2. Intravenous inoculation of C1300 cells led to multiple organ metastases including the liver, lung, kidney, ovary, lymph node and bone marrow. To examine the therapeutic effect of CTL in this metastasis model, CTL induced by parental or CD86 + C1300 cells were administrated into C1300-bearing mice. Adoptive transfer of CD86 + C1300-induced CTL resulted in marked elimination of multi-organ metastases and prolonged survival in almost all mice, 70% of which survived indefinitely. These results indicate that adoptive transfer of CTL induced by CD86-transfected tumor cells in vitro would be effective and useful for tumor immunotherapy against poorly immunogenic tumors.

  15. A single exercise bout enhances the manufacture of viral-specific T-cells from healthy donors: implications for allogeneic adoptive transfer immunotherapy

    PubMed Central

    Spielmann, Guillaume; Bollard, Catherine M.; Kunz, Hawley; Hanley, Patrick J.; Simpson, Richard J.

    2016-01-01

    Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections remain a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). The adoptive transfer of donor-derived viral-specific cytotoxic T-cells (VSTs) is an effective treatment for controlling CMV and EBV infections after HSCT; however, new practical methods are required to augment the ex vivo manufacture of multi-VSTs from healthy donors. This study investigated the effects of a single exercise bout on the ex vivo manufacture of multi-VSTs. PBMCs isolated from healthy CMV/EBV seropositive participants before (PRE) and immediately after (POST) 30-minutes of cycling exercise were stimulated with CMV (pp65 and IE1) and EBV (LMP2A and BMLF1) peptides and expanded over 8 days. The number (fold difference from PRE) of T-cells specific for CMV pp65 (2.6), EBV LMP2A (2.5), and EBV BMLF1 (4.4) was greater among the VSTs expanded POST. VSTs expanded PRE and POST had similar phenotype characteristics and were equally capable of MHC-restricted killing of autologous target cells. We conclude that a single exercise bout enhances the manufacture of multi-VSTs from healthy donors without altering their phenotype or function and may serve as a simple and economical adjuvant to boost the production of multi-VSTs for allogeneic adoptive transfer immunotherapy. PMID:27181409

  16. Antibody responses to allergen Lol pIV are suppressed following adoptive transfer of B lymphocytes from the internal image anti-idiotypic antibody-treated mice.

    PubMed

    Zhou, E M; Kisil, F T

    1995-10-01

    An internal image anti-idiotypic antibody, designated B1/1, was generated against an idiotope (Id91) of the monoclonal antibody (mAb91) specific for Lol pIV. The administration of B1/1 in PBS, at doses ranging from 100 ng to 100 micrograms/mouse, to syngeneic Balb/c mice resulted in the suppression of the formation of anti-Lol pIV antibodies that possessed the Id91. Spleen cells obtained from the mice 2 weeks after the treatment with B1/1 (25 micrograms/mouse) were adoptively transferred intravenously into the syngeneic recipients which were challenged intraperitoneally with Lol pIV in alum 2 hr after the transfer. The recipients were boosted with Lol pIV 14 days later. It was demonstrated that the transfer of splenic B cells (but not of T cells) from B1/1-treated donors induced a significant suppression of not only the level of IgE and IgG antibodies to Lol pIV, but also the level of antibodies possessing the Id91. Treatment of the B cells with mAb91 plus complement abrogated their ability to transfer the suppression. This study indicates that the treatment with the anti-Id B1/1 generated B cells that were characterized, serologically, as possessing the anti-Id-like antibodies on their surface and were responsible for transferring the suppression of the formation of antibodies to allergen Lol pIV and the expression of Id91.

  17. Superiority of rapamycin over tacrolimus in preserving nonhuman primate Treg half-life and phenotype after adoptive transfer.

    PubMed

    Singh, K; Stempora, L; Harvey, R D; Kirk, A D; Larsen, C P; Blazar, B R; Kean, L S

    2014-12-01

    Many critical issues remain concerning how best to deploy adoptive regulatory T cell (Treg) immunotherapy to the clinic. These include a determination of their pharmacokinetic characteristics, their optimal dose, their phenotypic stability and the best therapies with which to pair Tregs. By performing a CFSE-labeled autologous Treg pulse experiment, we determined that the accessible peripheral blood Treg pool in rhesus macaques is quite large (75 ± 11 × 10(6) Tregs/kg). Pharmacokinetic analysis revealed that Tregs have two phases of elimination: an α phase, with a T1/2 in the peripheral blood of 32.4 ± 11.3 h and a β phase with a T1/2 of 120.4 ± 19.7 h. In addition to their short initial half-life, Tregs underwent rapid phenotypic shifts after infusion, with significant loss of both CD25 and FoxP3 by day +6. While tacrolimus stabilized CD25 expression, it did not improve T1/2 , nor mitigate the loss of FoxP3. In contrast, rapamycin significantly stabilized both CD25 and FoxP3, and supported an increased half-life, with an α phase of 67.7 ± 6.9 h and a β phase of 252.1 ± 54.9 h. These results suggest that rapamycin may be a necessary addition to Treg immunotherapy, and that tacrolimus may be deleterious to Treg integrity posttransfer.

  18. Correlation of natural killer cell activity and clearance of Cryptococcus neoformans from mice after adoptive transfer of splenic nylon wool-nonadherent cells.

    PubMed Central

    Hidore, M R; Murphy, J W

    1986-01-01

    Previous reports demonstrate that natural killer (NK) cells inhibit the growth of Cryptococcus neoformans in vitro, but conclusive evidence supporting the effectiveness of NK cells in host resistance to cryptococci is not available. The objective of these studies was to assess the ability of NK cells to clear C. neoformans from the lungs, livers, and spleens of infected mice. CBA/J mice were depleted of NK cells, as well as other natural effector cells, by an intraperitoneal injection of cyclophosphamide (Cy), 240 mg/kg of body weight. One day later, 7.5 X 10(7) nylon wool-nonadherent (NWN) spleen cells, either untreated or treated with anti-asialo GM1 and complement to remove NK cells, were adoptively transferred to Cy-pretreated mice. On day 2 after Cy treatment, the mice were injected intravenously with 2 X 10(4) cryptococci. At 4 and 6 days after Cy treatment, tissues were assayed for NK reactivity, using a 4-h 51Cr-release assay, and for in vivo clearance of cryptococci as reflected by mean log10 CFU per organ. We observed that Cy treatment depleted NK activity against YAC-1 targets and reduced in vivo clearance of C. neoformans from the tissues of infected mice. Additionally, Cy treatment depleted the total lung and spleen cellularity and the total number of peripheral blood lymphocytes when compared with those in normal untreated control mice. Also, spleen weights were significantly decreased in comparison with those of untreated animals 4 days after Cy treatment. Adoptive transfer of untreated NWN spleen cells into Cy-depressed mice restored the NK cell activity which correlated with enhanced clearance of cryptococci from lungs, livers, and spleens. In contrast, treatment of NWN spleen cells with anti-asialo GM1 and complement before adoptive transfer abrogated the ability of these cells to restore NK activity or reduce the numbers of cryptococci present in tissues of infected mice. Taken together, these data indicate that NK cells are the cells effective

  19. Maternal Immunization Earlier in Pregnancy Maximizes Antibody Transfer and Expected Infant Seropositivity Against Pertussis

    PubMed Central

    Eberhardt, Christiane S.; Blanchard-Rohner, Geraldine; Lemaître, Barbara; Boukrid, Meriem; Combescure, Christophe; Othenin-Girard, Véronique; Chilin, Antonina; Petre, Jean; de Tejada, Begoña Martinez; Siegrist, Claire-Anne

    2016-01-01

    Background. Maternal immunization against pertussis is currently recommended after the 26th gestational week (GW). Data on the optimal timing of maternal immunization are inconsistent. Methods. We conducted a prospective observational noninferiority study comparing the influence of second-trimester (GW 13–25) vs third-trimester (≥GW 26) tetanus-diphtheria-acellular pertussis (Tdap) immunization in pregnant women who delivered at term. Geometric mean concentrations (GMCs) of cord blood antibodies to recombinant pertussis toxin (PT) and filamentous hemagglutinin (FHA) were assessed by enzyme-linked immunosorbent assay. The primary endpoint were GMCs and expected infant seropositivity rates, defined by birth anti-PT >30 enzyme-linked immunosorbent assay units (EU)/mL to confer seropositivity until 3 months of age. Results. We included 335 women (mean age, 31.0 ± 5.1 years; mean gestational age, 39.3 ± 1.3 GW) previously immunized with Tdap in the second (n = 122) or third (n = 213) trimester. Anti-PT and anti-FHA GMCs were higher following second- vs third-trimester immunization (PT: 57.1 EU/mL [95% confidence interval {CI}, 47.8–68.2] vs 31.1 EU/mL [95% CI, 25.7–37.7], P < .001; FHA: 284.4 EU/mL [95% CI, 241.3–335.2] vs 140.2 EU/mL [95% CI, 115.3–170.3], P < .001). The adjusted GMC ratios after second- vs third-trimester immunization differed significantly (PT: 1.9 [95% CI, 1.4–2.5]; FHA: 2.2 [95% CI, 1.7–3.0], P < .001). Expected infant seropositivity rates reached 80% vs 55% following second- vs third-trimester immunization (adjusted odds ratio, 3.7 [95% CI, 2.1–6.5], P < .001). Conclusions. Early second-trimester maternal Tdap immunization significantly increased neonatal antibodies. Recommending immunization from the second trimester onward would widen the immunization opportunity window and could improve seroprotection. PMID:26797213

  20. Whole-body imaging of adoptively transferred T cells using magnetic resonance imaging, single photon emission computed tomography and positron emission tomography techniques, with a focus on regulatory T cells

    PubMed Central

    Leech, J M; Sharif-Paghaleh, E; Maher, J; Livieratos, L; Lechler, R I; Mullen, G E; Lombardi, G; Smyth, L A

    2013-01-01

    Cell-based therapies using natural or genetically modified regulatory T cells (Tregs) have shown significant promise as immune-based therapies. One of the main difficulties facing the further advancement of these therapies is that the fate and localization of adoptively transferred Tregs is largely unknown. The ability to dissect the migratory pathway of these cells in a non-invasive manner is of vital importance for the further development of in-vivo cell-based immunotherapies, as this technology allows the fate of the therapeutically administered cell to be imaged in real time. In this review we will provide an overview of the current clinical imaging techniques used to track T cells and Tregs in vivo, including magnetic resonance imaging (MRI) and positron emission tomography (PET)/single photon emission computed tomography (SPECT). In addition, we will discuss how the finding of these studies can be used, in the context of transplantation, to define the most appropriate Treg subset required for cellular therapy. PMID:23574314

  1. Policy Borrowing and Transfer, and Policy Convergence: Justifications for the Adoption of the Bologna Process in the CEMAC Region and the Cameroonian Higher Education System through the LMD Reform

    ERIC Educational Resources Information Center

    Eta, Elizabeth Agbor

    2015-01-01

    The borrowing and transfer of policies, ideas and practices from one system to another may in part explain the convergence of educational systems. Using text documents as research material, this paper examines the adoption and transfer of Bologna Process (BP) ideas in the Economic and Monetary Community of Central Africa (CEMAC) and in the…

  2. Transfer of immunity against lethal murine Francisella infection by specific antibody depends on host gamma interferon and T cells.

    PubMed Central

    Rhinehart-Jones, T R; Fortier, A H; Elkins, K L

    1994-01-01

    Both serum and spleen cells from mice immune to Francisella tularensis transfer protection to naive recipients. Here we characterize the mechanism of protection induced by transfer of immune mouse serum (IMS). IMS obtained 4 weeks after intradermal infection with 10(3) bacteria of the live vaccine strain (LVS) contained high levels of immunoglobulin G2 (IgG2a) and IgM (end point titers, 1:16,600 and 1:7,200, respectively) and little IgG1, IgG2b, or IgG3. LVS-specific antibodies were detected 5 days after intradermal infection, and reached peak levels by 2 weeks postinfection. Only sera obtained 10 days or more after sublethal infection, when IgG titers peaked, transferred protection against a challenge of 100 50% lethal doses (LD50s). Purified high-titer IgG anti-LVS antibody but not IgM anti-LVS antibody was responsible for transfer of protection against an intraperitoneal challenge of up to 3,000 LD50s. IMS had no direct toxic effects on LVS and did not affect uptake or growth of bacteria in association with peritoneal cells. One day after LVS infection, liver, spleen, and lung tissue from mice treated with IMS contained 1 to 2 log units fewer bacteria than did tissue from mice treated with normal mouse serum or phosphate-buffered saline. Between 2 and 4 days after infection, however, bacterial growth rates in tissues were similar in both serum-protected mice and unprotected mice. Bacterial burdens in IMS-treated, LVS-infected mice declined in infected tissues after day 5, whereas control animals died. This lag phase suggested that development of a host response was involved in complete bacterial clearance. In fact, transfer of IMS into normal recipients that were simultaneously treated with anti-gamma interferon and challenged with LVS did not protect mice from death. Further, transfer of IMS into athymic nu/nu mice did not protect against LVS challenge; protection was, however, reconstituted by transfer of normal T cells into nu/nu mice. Thus, "passive

  3. Efficient tumor regression by adoptively transferred CEA-specific CAR-T cells associated with symptoms of mild cytokine release syndrome

    PubMed Central

    Wang, Linan; Ma, Ning; Okamoto, Sachiko; Amaishi, Yasunori; Sato, Eiichi; Seo, Naohiro; Mineno, Junichi; Takesako, Kazutoh; Kato, Takuma; Shiku, Hiroshi

    2016-01-01

    ABSTRACT Carcinoembryonic antigen (CEA) is a cell surface antigen highly expressed in various cancer cell types and in healthy tissues. It has the potential to be a target for chimeric antigen receptor (CAR)-modified T-cell therapy; however, the safety of this approach in terms of on-target/off-tumor effects needs to be determined. To address this issue in a clinically relevant model, we used a mouse model in which the T cells expressing CEA-specific CAR were transferred into tumor-bearing CEA-transgenic (Tg) mice that physiologically expressed CEA as a self-antigen. The adoptive transfer in conjunction with lymphodepleting and myeloablative preconditioning mediated significant tumor regression but caused weight loss in CEA-Tg, but not in wild-type mice. The weight loss was not associated with overt inflammation in the CEA-expressing gastrointestinal tract but was associated with malnutrition, reflected in elevated systemic levels of cytokines linked to anorexia, which could be controlled by the administration of an anti-IL-6 receptor monoclonal antibody without compromising efficacy. The apparent relationship between lymphodepleting and myeloablative preconditioning, efficacy, and off-tumor toxicity of CAR-T cells would necessitate the development of CEA-specific CAR-T cells with improved signaling domains that require less stringent preconditioning for their efficacy. Taken together, these results suggest that CEA-specific CAR-based adoptive T-cell therapy may be effective for patients with CEA+ solid tumors. Distinguishing the fine line between therapeutic efficacy and off-tumor toxicity would involve further modifications of CAR-T cells and preconditioning regimens. PMID:27757303

  4. Training substance abuse treatment organizations to adopt evidence-based practices: the Addiction Technology Transfer Center of New England Science to Service Laboratory.

    PubMed

    Squires, Daniel D; Gumbley, Stephen J; Storti, Susan A

    2008-04-01

    Underutilization of evidence-based treatments for substance abuse represents a longstanding problem for the field and the public health of our nation. Those who would most benefit from research advances (community treatment agencies and the clients they serve) have historically been the least likely to be exposed to innovative evidence-based methods for substance abuse treatment. To help address this gap, the Addiction Technology Transfer Center of New England (ATTC-NE), located at Brown University, has adapted and implemented an organizational change strategy intended to equip substance abuse treatment organizations and their employees with the skills needed to adopt evidence-based treatment practices. Since 2003, the ATTC-NE has worked with 54 community-based substance abuse treatment agencies from across New England using this model, which is called Science to Service Laboratory (SSL). Twenty-eight of 54 agencies completed all of the SSL components, and 26 of these 28 completer agencies (96%) successfully adopted and implemented contingency management as a result. Survey data comparing completer and dropout agencies' satisfaction with the quality, organization, and utility of the SSL indicate that both groups rated the SSL favorably. However, differences emerged with respect to organizational characteristics between completer and dropout agencies. Specifically, dropout agencies were more likely to report turnover in staff positions vital to training effort. Future directions for the model are discussed.

  5. Successful immunotherapy of natural killer-resistant established pulmonary melanoma metastases by the intravenous adoptive transfer of syngeneic lymphocytes activated in vitro by interleukin 2

    PubMed Central

    1984-01-01

    In previous in vitro studies, we have shown that murine splenocytes or cancer patient lymphocytes incubated in IL-2 become lytic for fresh syngeneic or autologous tumors. We have now performed the adoptive transfer of such lymphokine-activated killer (LAK) cells in a murine B16 metastasis model to test their in vivo efficacy. 1 X 10(8) LAK cells, infused intravenously into C57BL/6 mice with established B16 pulmonary metastases, led to a marked decreased in the number of lung nodules and improved survival. LAK cells administered 3 d after amputation of a tumor-bearing limb also decreased the incidence of spontaneous pulmonary metastases. LAK cells generated from tumor-bearer splenocytes had effects equivalent to those from normal animals, and this antimetastatic effect of the LAK cells did not require the prior administration of cyclophosphamide or other immunosuppressants. Fresh or unstimulated splenocytes had no effect. The antitumor effectors and precursors in vivo and in vitro were Thy-1+. The lymphokine required for the activation appeared to be interleukin 2 (IL-2), since incubation in partially purified supernatants from PMA pulsed EL-4 or Con A-pulsed splenocytes or purified Jurkat IL-2 led to the generation of LAK cells equally active in vivo. The use of IL-2-activated cells may provide a valuable method for the adoptive therapy of human neoplasms as well. PMID:6141211

  6. Immune responses to adenoviral vectors during gene transfer in the brain.

    PubMed

    Kajiwara, K; Byrnes, A P; Charlton, H M; Wood, M J; Wood, K J

    1997-02-10

    We have investigated the immune response to E1-deleted adenovirus vectors encoding the lacZ gene introduced into the brains of adult mice. Injection of these nonreplicating vectors caused a marked inflammatory response in the brain as assessed by immunocytochemistry and flow cytometry of leukocytes. Infiltrating leukocytes were detectable within 2 days of injection and reached a maximum by 9 days. Thereafter, the number of infiltrating cells decreased, but a small number persisted in the brain until day 60. Between 2 and 4 days after injection, the percentage of CD8+ cells detectable increased whereas the percentage of CD4+ cells present in the infiltrating population did not significantly increase until day 6, peaking on day 15. Activated CD25+ T cells were detectable between days 6 and 15. beta-Galactosidase (beta-Gal), the product of the lacZ gene encoded by the vector, was also detected, both at the injection site in the striatum and also in the substantia nigra. Expression peaked between 4 and 6 days but a small number of beta-Gal+ cells was still seen at 60 days after injection. This study demonstrates that a quantitative analysis of the immune responses caused by a nonreplicating adenovirus vector is possible in the brain. E1-deleted adenoviral vectors trigger a strong inflammatory response in the brain, but this immune response is not sufficient to eliminate completely expression of genes encoded by the adenoviral construct. PMID:9048192

  7. Evaluation of a commercial bovine colostrum replacer for achieving passive transfer of immunity in springbok calves (Antidorcas marsupialis).

    PubMed

    Thompson, Kimberly A; Lamberski, Nadine; Kass, Philip H; Coons, David; Chigerwe, Munashe

    2013-09-01

    Failure of passive transfer (FPT) occurs in ruminant species when there is inadequate absorption of immunoglobulins from the colostrum. In zoologic establishments, FPT can be a common occurrence in hand-raised ruminant neonates fed insufficient amounts of colostrum replacer (CR) and/or poor-quality CR. The goals of this study were to investigate the efficacy of a commercial bovine CR at achieving adequate passive transfer of immunity and evaluate tests to assess FPT in nondomestic ruminant species. In the past several years, research in dairy calves has shown that passive transfer rates can be dramatically improved if the CR dose is doubled. The treatment group (n = 10) consisted of springbok (Antidorcas marsupialis) calves fed Land O'Lakes bovine commercial CR at a dose of > or = 4.68 g of immunoglobulin G (22 g of CR powder) per kilogram of animal's body weight divided into five feedings over 24 hr. The control group (n=7) consisted of calves that nursed from their dams. This study reported no significant difference between the proportion of calves with adequate passive transfer in the treatment (80%) and control (71%) groups (P= 1.00). Morbidity and mortality rates until weaning were 0% in both groups. The study also determined the sensitivity and specificity values (n = 37) for five serum tests (y-glutamyl-transferase [GGT], globulin, glutaraldehyde coagulation [GC], sodium sulfite turbidity test, and total protein) used to determine passive transfer status in springbok calves. This study recommends the following serum tests and cutoff ranges for determining FPT in springbok calves: globulin < or = 1.85 mg/dl, GGT < or = 228.5 IU/ L, and GC > or = 28 min. PMID:24063080

  8. Adoptive cell transfer of contact sensitivity-initiation mediated by nonimmune cells sensitized with monoclonal IgE antibodies. Dependence on host skin mast cells.

    PubMed

    Matsuda, H; Ushio, H; Paliwal, V; Ptak, W; Askenase, P W

    1995-05-15

    A role for mast cell release of serotonin (5-HT), via Ag-specific factors derived from Thy-1+ B220+ lymphoid cells in the initiation of murine contact sensitivity (CS) has been suggested. However, because CS in mast cell-deficient mice was intact, a role for mast cells in CS initiation was unclear. Therefore, we examined whether CS could be initiated by i.v. injection of nonimmune mixed lymphoid cells that were sensitized in vitro with IgE. When naive mice received IgE-sensitized nonimmune spleen or lymph node cells, or IgE-sensitized purified mast cells, together with immune CS-effector B220- T cells, which therefore were depleted of CS-initiating, Thy-1+, B220+ cells, which could not transfer CS, then reconstitution of CS occurred. Mast cell-deficient W/Wv mice could not elicit this IgE-dependent CS ear swelling, but when mast cell deficiency was reversed by ear injection of normal bone marrow-derived cultured mast cells, then CS was restored. In vitro pretreatment with irrelevant monoclonal anti-OVA IgE prevented CS initiation mediated by Ag-specific, IgE mAb-sensitized cells, presumably by blocking sensitization with IgE. Thus Fc epsilon R on the normal lymphoid cells were involved. When ketanserin, a 5-HT2 receptor antagonist, was injected i.v. before cell transfer, CS initiation via IgE-sensitized cells and CS were no longer elicited. Thus, in this system, IgE Abs bound to circulating IgE Fc epsilon R bearing lymphoid cells sensitized in vitro (most likely basophils), probably mediated early activation of these circulating basophils to release mediators, causing 5-HT release from cutaneous mast cells, to mediate CS initiation. PMID:7730614

  9. [In vitro transfer of immunity against PPD with dialyzable extract of leukocytes from human colostrum].

    PubMed

    Martínez-Cairo Cueto, S; Alasio-Chávez, C; Dávila Velázquez, J R

    1992-01-01

    The aim of this study is to demonstrate the transference of PPD hypersensibility in an in vitro model, with dialysable colostral leukocyte extract (DCLE) of PPD+ and PPD-mothers, through measurements of leukocyte migration inhibition factor activity (LIF) from blood obtained of the umbilical cord of newborns from PPD+ mothers. The results show that DCLE PPD+ incubated with leukocytes of newborns from PPD- mothers had inhibition of leukocyte migration compared with migration of leukocytes incubated with DCLE PPD-. These results suggest that in this in vitro model, DCLE transfers hypersensibility to PPD. PMID:1492196

  10. Cytotoxic T lymphocyte antigen 4 decreases humoral and cellular immunity by adenovirus to enhance target GFP gene transfer in C57BL/6 mice.

    PubMed

    Bai, Dou; Zhu, Wei; Zhang, Yu; Long, Ling; Zhu, Naishuo

    2015-01-01

    Adenoviruses (Ad) are once potential and promising vectors for gene delivery, but the immunogenicity attenuates its transfer efficiency. Cytotoxic T lymphocyte antigen 4 (CTLA-4) can inhibit T cell immunity. Thus, we aimed to study the effect of CTLA-4 in the process of Ad-mediated gene transfer. The C57BL/6 mice were injected by Ad vectors at twice, and CTLA-4 was administrated after the first Ad injection. Then, the CD3(+)CD4(+) T cells and circulating levels of IL-2, IL-4, and anti-Ad IgG were decreased by CTLA-4, while Ad generated immune responses. The green fluorescence protein (GFP) expressions of tissues were enhanced by CTLA-4 till injection of Ad at twice. Our results indicate that CTLA-4 can inhibit humoral and cellular immunity by adenovirus generation to enhance GFP delivery, and provide a potential way to assist in Ad-mediated gene transfer.

  11. Antigen Transfer from Exosomes to Dendritic Cells as an Explanation for the Immune Enhancement Seen by IgE Immune Complexes

    PubMed Central

    Henningsson, Frida; Heyman, Birgitta; Conrad, Daniel H.

    2014-01-01

    IgE antigen complexes induce increased specific T cell proliferation and increased specific IgG production. Immediately after immunization, CD23+ B cells capture IgE antigen complexes, transport them to the spleen where, via unknown mechanisms, dendritic cells capture the antigen and present it to T cells. CD23, the low affinity IgE receptor, binds IgE antigen complexes and internalizes them. In this study, we show that these complexes are processed onto B-cell derived exosomes (bexosomes) in a CD23 dependent manner. The bexosomes carry CD23, IgE and MHC II and stimulate antigen specific T-cell proliferation in vitro. When IgE antigen complex stimulated bexosomes are incubated with dendritic cells, dendritic cells induce specific T-cell proliferation in vivo, similar to IgE antigen complexes. This suggests that bexosomes can provide the essential transfer mechanism for IgE antigen complexes from B cells to dendritic cells. PMID:25330118

  12. Aerosol Delivery of Interleukin-2 in Combination with Adoptive Transfer of Natural Killer Cells for the Treatment of Lung Metastasis: Methodology and Effect.

    PubMed

    Kiany, Simin; Gordon, Nancy

    2016-01-01

    Natural killer (NK) cells are a subtype of lymphocytes with a major role as a host defense mechanism against tumor cells. Allogeneic NK cell therapy is being used as an alternative promising therapy for many different cancers. Interleukin-2 (IL-2) is a critical cytokine for NK cell proliferation, survival, and effector functions. Cytokine support is essential to activate, expand, and increase the life span of NK cells. Aerosol delivery of IL-2 in combination with adoptive transfer of NK cells offers a reasonable approach for the treatment of lung metastases as it avoids the deleterious side effects of systemic IL-2. Using a human OS mouse model, we demonstrated the efficacy of this approach. Combination therapy of aerosol IL-2 with NK cells resulted in a better therapeutic effect against OS lung metastases as compared with each therapy alone. Aerosol IL-2 selectively increased infiltration, retention, and proliferation of infused NK cells in the lung, and there was no local inflammation or toxicity in the lungs or any other organ. Our results demonstrate that delivery of IL-2 via the aerosol route offers a feasible and innovative approach to enhance the immunotherapeutic effect of NK cells against pulmonary metastases. In the following chapter, we describe the methodology and effect of this innovative therapeutic approach. PMID:27177675

  13. Effects of newborn characteristics and length of colostrum feeding period on passive immune transfer in goat kids.

    PubMed

    Castro, N; Capote, J; Morales-Delanuez, A; Rodríguez, C; Argüello, A

    2009-04-01

    Majorera goat kids (n = 200) were used to evaluate the effects of litter size, birth body weight, sex, and suckling duration on serum IgG concentrations. Kids were assigned to 1 of 3 experimental groups: litter size and sex were equally distributed in each group. In the first group, kids (n = 67) stayed with their dams for 24 h; in the second group, kids (n = 66) stayed with their dams for 48 h; and in the third group, kids (n = 67) stayed with their dams for 120 h. Blood samples were obtained every 24 h for 5 d, and serum IgG concentration was measured using radial immunodiffusion. In litter sizes of 1 to 2 kids, IgG blood serum concentration was significantly higher (18.30 +/- 5.40 mg/mL) than in litters of 3 kids (9.85 +/- 4.23 mg/mL). Kid sex did not affect IgG blood serum concentrations. Suckling duration did not affect kid serum IgG concentrations. In conclusion, kids with low birth body weight (<2.8 kg) or from litters of 3 may need special attention. If newborn goat kids are allowed to suckle colostrum for at least 24 h from their dams, this seems to be sufficient time to ingest enough IgG from colostrum to achieve an adequate serum IgG concentration and passive immune protection to avoid failure of passive immune transfer.

  14. The Cellular Immune Mechanism after Transfer of Chemically Extracted Acellular Nerve Xenografts

    PubMed Central

    Lin, Xingshi; Yang, Ruojia; He, Qing; Ruan, Dike

    2013-01-01

    Severe peripheral nerve defect by injuries causing functional loss require nerve grafting. Autograft has limitations for clinical use because it results in the creation of a new nerve injury and the generation of donor site morbidity. Based on these limitations, nerve allografts and xenografts provide a readily accessible alternative strategy. The aim of the present study was to observe the immune mechanism underlying the rejection of chemically extracted acellular nerve xenografts, and further evaluate immunogenicity of chemically treated acellular nerve grafts for clinical applications. A total of 160 BALB/c mice were randomly divided into a negative contrast group (NC, 40 mice), a fresh autograft group (AG, 40 mice), a fresh xenogeneic nerve group (FXN, 40 mice) and a chemically extracted acellular xenogeneic nerve group (CEXN, 40 mice). Various types of nerve grafts were implanted into the thigh muscle of BALB/C mice in the corresponding groups. At 3, 7, 14 and 28 days post-operation, the mice (10 mice from each group) were sacrificed and their spleens were extracted. The spleens were ground into paste. The erythrocytes and other cells were lysed using distilled water and the T lymphocytes were collected. Fluorescein isothiocyanate (FITC) -labeled monoclonal antibodies (CD3, CD4, CD8, CD25, IL-2, IFN-γ and TNF-α) were then added to the solution. The Fluorescence Activated Cell Sorting (FACS) was used to determine the positivity rate of the cells combined with the monoclonal antibodies above. No significant statistical differences were observed between the CEXN, NC and AG groups, so that no obvious immune rejections were observed among the chemically extracted acellular nerve xenografts. PMID:23874771

  15. The Skeletal Muscle Environment and Its Role in Immunity and Tolerance to AAV Vector-Mediated Gene Transfer.

    PubMed

    Boisgerault, Florence; Mingozzi, Federico

    2015-01-01

    Since the early days of gene therapy, muscle has been one the most studied tissue targets for the correction of enzyme deficiencies and myopathies. Several preclinical and clinical studies have been conducted using adeno-associated virus (AAV) vectors. Exciting progress has been made in the gene delivery technologies, from the identification of novel AAV serotypes to the development of novel vector delivery techniques. In parallel, significant knowledge has been generated on the host immune system and its interaction with both the vector and the transgene at the muscle level. In particular, the role of underlying muscle inflammation, characteristic of several diseases affecting the muscle, has been defined in terms of its potential detrimental impact on gene transfer with AAV vectors. At the same time, feedback immunomodulatory mechanisms peculiar of skeletal muscle involving resident regulatory T cells have been identified, which seem to play an important role in maintaining, at least to some extent, muscle homeostasis during inflammation and regenerative processes. Devising strategies to tip this balance towards unresponsiveness may represent an avenue to improve the safety and efficacy of muscle gene transfer with AAV vectors.

  16. The Skeletal Muscle Environment and Its Role in Immunity and Tolerance to AAV Vector-Mediated Gene Transfer

    PubMed Central

    Boisgérault, Florence; Mingozzi, Federico

    2015-01-01

    Since the early days of gene therapy, muscle has been one the most studied tissue targets for the correction of enzyme deficiencies and myopathies. Several preclinical and clinical studies have been conducted using adeno-associated virus (AAV) vectors. Exciting progress has been made in the gene delivery technologies, from the identification of novel AAV serotypes to the development of novel vector delivery techniques. In parallel, significant knowledge has been generated on the host immune system and its interaction with both the vector and the transgene at the muscle level. In particular, the role of underlying muscle inflammation, characteristic of several diseases affecting the muscle, has been defined in terms of its potential detrimental impact on gene transfer with AAV vectors. At the same time, feedback immunomodulatory mechanisms peculiar of skeletal muscle involving resident regulatory T cells have been identified, which seem to play an important role in maintaining, at least to some extent, muscle homeostasis during inflammation and regenerative processes. Devising strategies to tip this balance towards unresponsiveness may represent an avenue to improve the safety and efficacy of muscle gene transfer with AAV vectors. PMID:26122097

  17. Antibody transferred from the blood to the gastrointestinal tract and its role in enteric immunity of neonatal calves

    SciTech Connect

    Besser, T.E.

    1986-01-01

    High passive blood immunoglobulin concentrations are associated with decreased infectious enteric disease mortality in neonatal calves. Passive immunoglobulin transferred from the blood to the gastrointestinal tract may explain this protection. To measure the rate at which immunoglobulin G/sub 1/ (IgG/sub 1/) is transferred to the gastrointestinal tract, /sup 125/I-labelled bovine IgG/sub 1/ anti-DNP antibody was administered to calves by intravenous injection. The clearance rate of /sup 125/I-IgG/sub 1/ from the blood was measured and compared to the rate of /sup 125/I-IgG/sub 1/ appearance in the gastrointestinal tract, as measured (1) by the rate of fecal /sup 125/I-IgG/sub 1/ excretion, and (2) by the amount of /sup 125/I-IgG/sub 1/ in the gastrointestinal tract of calves at necropsy. Rotavirus antibody titers in the gastrointestinal contents of 5- and 10-days-old calves correlated with the calves' serum passive rotavirus antibody titers, and were increased in proportion to the amount of colostral antibody fed on the first day of life. In contrast, when colostral rotavirus antibody was fed to 48-hour-old calves, when absorption of passive immunoglobulin does not occur, there was no measurable increase in antibody in the intestine 5 days later. Intestinal antibody in the 5- and 10-day-old calves therefore resulted from blood antibody transferred to the gastrointestinal tract. Rotavirus antibody administered to calves by parenteral injection protected them from infection and diarrhea after rotavirus challenge. These results indicate that passive blood IgG enters the calf gastrointestinal tract, where it contributes to intestinal immunity.

  18. In vivo imaging and quantitation of adoptively transferred human antigen-specific T cells transduced to express a human norepinephrine transporter gene.

    PubMed

    Doubrovin, Mikhail M; Doubrovina, Ekaterina S; Zanzonico, Pat; Sadelain, Michel; Larson, Steven M; O'Reilly, Richard J

    2007-12-15

    Sequential imaging of genetically marked effector cells after adoptive transfer in vivo has greatly enhanced analyses of their biodistribution, growth, and activity both in animal models and in clinical trials of cellular immunotherapy. However, the immunogenicity of cells expressing xenogeneic reporter constructs limits their survival and clinical utility. To address this limitation, we have evaluated a human norepinephrine transporter (hNET) permitting imaging of transduced cells in vivo with a previously approved clinical grade radiolabeled probe, metaiodobenzylguanidine (MIBG). The hNET gene cDNA was cloned from the SK-N-SH cell line and inserted into a bicistronic retroviral vector also encoding green fluorescent protein. Following transfection, human EBV-specific T lymphocytes seemed fully functional in vitro and also selectively accumulated [(123)I]MIBG. In nonobese diabetic/severe combined immunodeficient mice bearing human EBV lymphoma xenografts, as few as 10(4) transduced T cells injected into the tumors could be imaged by single-photon emission computed tomography (SPECT) or positron emission tomography (PET) after i.v. infusion of [(123)I]MIBG or [(124)I]MIBG, respectively. When hNET(+) EBV-specific T cells were infused i.v., their migration and specific accumulation in EBV(+) tumors expressing their restricting HLA allele could be imaged by SPECT or PET over 28 days. Image intensity was closely correlated with the number of T cells accumulated in targeted tumors. The use of two reporter probes (MIBG and 2'-deoxy-2'-fluoro-beta-d-arabinofuranosyl-5-iodouracil) permitted independent contemporaneous tracking of two distinct EBV-specific T-cell subpopulations expressing different reporter genes (hNET-CD4(+) T cells and HSV-TK-CD8(+) T cells) in the same animal using three-dimensional nuclear modalities (SPECT and PET). The hNET-based system described may thus have significant potential as a nonimmunogenic reporter for extended repeated quantitative in

  19. Phase I Trial of Adoptive Cell Transfer with Mixed-Profile Type-I/Type-II Allogeneic T Cells for Metastatic Breast Cancer

    PubMed Central

    Hardy, Nancy M.; Mossoba, Miriam E.; Steinberg, Seth M.; Fellowes, Vicki; Yan, Xiao-Yi; Hakim, Frances T.; Babb, Rebecca R.; Avila, Daniele; Gea-Banacloche, Juan; Sportès, Claude; Levine, Bruce L.; June, Carl H.; Khuu, Hahn M.; Carpenter, Ashley E.; Krumlauf, Michael C.; Dwyer, Andrew J.; Gress, Ronald E.; Fowler, Daniel H.; Bishop, Michael R.

    2011-01-01

    PURPOSE Metastatic breast cancer (MBC) response to allogeneic lymphocytes requires donor T-cell engraftment and is limited by graft-versus-host disease (GVHD). In mice, Type-II-polarized T cells promote engraftment and modulate GVHD whereas Type-I-polarized T cells mediate more potent graft-versus-tumor (GVT) effects. This Phase-I translational study evaluated adoptive transfer of ex-vivo-costimulated Type-I/Type-II (T1/T2) donor T cells with T-cell-depleted (TCD) allogeneic stem-cell transplantation (AlloSCT) for MBC. EXPERIMENTAL DESIGN Patients had received anthracycline, taxane and antibody therapies, been treated for metastatic disease and an HLA-identical-sibling donor. Donor lymphocytes were costimulated ex vivo with anti-CD3/anti-CD28 antibody-coated magnetic beads in IL-2/IL-4-supplemented media. Patients received reduced-intensity conditioning, donor stem cells and T1/T2 cells, and monitoring for toxicity, engraftment, GVHD and tumor response; results were compared with historical controls, identically treated except for T1/T2-product infusions. RESULTS Mixed Type-I/Type-II CD4+-T cells predominated in T1/T2 products. Nine patients received T1/T2 cells at Dose-Level 1 (5×106 cells/kg). T-cell donor chimerism reached 100% by a median of 28 days. Seven (78%) developed acute GVHD. At Day +28, five patients had partial responses (56%) and none had MBC progression; thereafter, two patients had continued responses. Donor-T-cell engraftment and tumor responses appeared faster than in historical controls, but GVHD rates were similar and responders progressed early, often following treatment of acute GVHD. CONCLUSION Allogeneic T1/T2 cells were safely infused with TCD-AlloSCT, appeared to promote donor engraftment, and may have contributed to transient early tumor responses. PMID:21948234

  20. Exosomes secreted by nematode parasites transfer small RNAs to mammalian cells and modulate innate immunity.

    PubMed

    Buck, Amy H; Coakley, Gillian; Simbari, Fabio; McSorley, Henry J; Quintana, Juan F; Le Bihan, Thierry; Kumar, Sujai; Abreu-Goodger, Cei; Lear, Marissa; Harcus, Yvonne; Ceroni, Alessandro; Babayan, Simon A; Blaxter, Mark; Ivens, Alasdair; Maizels, Rick M

    2014-11-25

    In mammalian systems RNA can move between cells via vesicles. Here we demonstrate that the gastrointestinal nematode Heligmosomoides polygyrus, which infects mice, secretes vesicles containing microRNAs (miRNAs) and Y RNAs as well as a nematode Argonaute protein. These vesicles are of intestinal origin and are enriched for homologues of mammalian exosome proteins. Administration of the nematode exosomes to mice suppresses Type 2 innate responses and eosinophilia induced by the allergen Alternaria. Microarray analysis of mouse cells incubated with nematode exosomes in vitro identifies Il33r and Dusp1 as suppressed genes, and Dusp1 can be repressed by nematode miRNAs based on a reporter assay. We further identify miRNAs from the filarial nematode Litomosoides sigmodontis in the serum of infected mice, suggesting that miRNA secretion into host tissues is conserved among parasitic nematodes. These results reveal exosomes as another mechanism by which helminths manipulate their hosts and provide a mechanistic framework for RNA transfer between animal species.

  1. Adoptive cellular therapy.

    PubMed

    Grupp, Stephan A; June, Carl H

    2011-01-01

    Cell-based therapies with various lymphocytes and antigen-presenting cells are promising approaches for cancer immunotherapy. The transfusion of T lymphocytes, also called adoptive cell therapy (ACT), is an effective treatment for viral infections, has induced regression of cancer in early stage clinical trials, and may be a particularly important and efficacious modality in the period following hematopoietic stem cell transplantation (HSCT). Immune reconstitution post-SCT is often slow and incomplete, which in turn leads to an increased risk of infection and may impact relapse risk in patients with malignant disease. Immunization post-HSCT is frequently unsuccessful, due to the prolonged lymphopenia, especially of CD4 T cells, seen following transplant. ACT has the potential to enhance antitumor and overall immunity, and augment vaccine efficacy in the post-transplant setting. The ability to genetically engineer lymphocyte subsets has the further potential to improve the natural immune response, correct impaired immunity, and redirect T cells to an antitumor effector response. This chapter focuses on various applications of ACT for cancer immunotherapy, and we discuss some of the latest progress and hurdles in translating these technologies to the clinic.

  2. Protection against Mycobacterium tuberculosis infection by adoptive immunotherapy. Requirement for T cell-deficient recipients

    SciTech Connect

    Orme, I.M.; Collins, F.M.

    1983-07-01

    The results of this study demonstrate that spleen cells taken from mice at the height of the primary immune response to intravenous infection with Mycobacterium tuberculosis possess the capacity to transfer adoptive protection to M. tuberculosis-infected recipients, but only if these recipients are first rendered T cell-deficient, either by thymectomy and gamma irradiation, or by sublethal irradiation. A similar requirement was necessary to demonstrate the adoptive protection of the lungs after exposure to an acute aerosol-delivered M. tuberculosis infection. In both infectious models successful adoptive immunotherapy was shown to be mediated by T lymphocytes, which were acquired in the donor animals in response to the immunizing infection. It is proposed that the results of this study may serve as a basic model for the subsequent analysis of the nature of the T cell-mediated immune response to both systemic and aerogenic infections with M. tuberculosis.

  3. Effects of transgene expression level per cell in mice livers on induction of transgene-specific immune responses after hydrodynamic gene transfer.

    PubMed

    Yin, Y; Takahashi, Y; Hamana, A; Nishikawa, M; Takakura, Y

    2016-07-01

    We previously showed that high and sustained transgene expression of antigenic proteins induced transgene-specific immune responses. In the present study, a detailed relationship between the level of transgene expression per cell and immune response after hydrodynamic gene transfer was investigated. Cypridina luciferase (cLuc), a secretory antigenic reporter protein, was selected as a model antigen, and pROSA-cLuc, a plasmid expressing cLuc, was constructed. A fixed dose (30 μg) of pROSA-cLuc was delivered to mice by a single hydrodynamic injection or three injections at 24-h intervals because the number of cells transfected with plasmids is dependent on the number of hydrodynamic injections. Serum cLuc activity, an indicator of the total amount of cLuc transgene expression, was almost equal between these two groups. In contrast, the high-dose single injection induced higher levels of cLuc-specific humoral and cellular immune responses than the three low-dose injections. Moreover, the serum cLuc activity of the high-dose single injection group began to decline ~10 days after injection, whereas the activity remained constant in the three low-dose injection group. These results indicate that it is preferable to reduce the level of transgene expression per cell to avoid induction of the transgene-specific immune response after hydrodynamic gene transfer. PMID:26966861

  4. Experimental Salmonellosis XI. Induction of Cellular Immunity and Formation of Antibody by Transfer Agent of Mouse Mononuclear Phagocytes

    PubMed Central

    Mitsuhashi, Susumu; Saito, Kazuko; Osawa, Nobutaka; Kurashige, Satonori

    1967-01-01

    When mice were injected intraperitoneally with a ribonucleic acid (RNA) preparation extracted from the peritoneal mononuclear phagocytes (termed monocytes) of immunized mice, these macrophages developed cellular immunity and cellular antibodies. The peritoneal monocytes were obtained from normal mice and maintained in tissue culture bottles in a homogeneous cell population. When they were treated in vitro with an immune RNA preparation, they acquired cellular immunity, and cellular antibodies were detectable in such monocytes. These results suggest that the mononuclear phagocytic cell line constitutes a cell line responsible for antibody formation. PMID:6051363

  5. Maternal immunization

    PubMed Central

    Moniz, Michelle H; Beigi, Richard H

    2014-01-01

    Maternal immunization holds tremendous promise to improve maternal and neonatal health for a number of infectious conditions. The unique susceptibilities of pregnant women to infectious conditions, as well as the ability of maternally-derived antibody to offer vital neonatal protection (via placental transfer), together have produced the recent increased attention on maternal immunization. The Advisory Committee on Immunization Practices (ACIP) currently recommends 2 immunizations for all pregnant women lacking contraindication, inactivated Influenza and tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap). Given ongoing research the number of vaccines recommended during pregnancy is likely to increase. Thus, achieving high vaccination coverage of pregnant women for all recommended immunizations is a key public health enterprise. This review will focus on the present state of vaccine acceptance in pregnancy, with attention to currently identified barriers and determinants of vaccine acceptance. Additionally, opportunities for improvement will be considered. PMID:25483490

  6. The presence and preferential activation of Tregs diminishes adoptive transfer of autoimmune diabetes by polyclonal NOD T cell effectors into NSG versus NOD-scid mice1

    PubMed Central

    Presa, Maximiliano; Chen, Yi-Guang; Grier, Alexandra E.; Leiter, Edward H.; Brehm, Michael A.; Greiner, Dale L.; Shultz, Leonard D.; Serreze, David V.

    2015-01-01

    NOD-scid.Il2rgnull (NSG) mice are currently being used as recipients to screen for pathogenic autoreactive T-cells in Type 1 Diabetes (T1D) patients. We questioned whether the restriction of IL-2 receptor gamma chain (Il-2rγ) dependent cytokine signaling only to donor cells in NSG recipients differently influenced the activities of transferred diabetogenic T-cells when they were introduced as a monoclonal/oligoclonal population versus being part of a polyclonal repertoire. Unexpectedly, a significantly decreased T1D transfer by splenocytes from prediabetic NOD donors was observed in Il2rγnull -NSG versus Il2rγ-intact standard NOD-scid recipients. In contrast, NOD-derived monoclonal/oligoclonal TCR transgenic ß-cell autoreactive T-cells in either the CD8 (AI4, NY8.3) or CD4 (BDC2.5) compartments transferred disease significantly more rapidly to NSG than to NOD-scid recipients. The reduced diabetes transfer efficiency by polyclonal T cells in NSG recipients was associated with enhanced activation of regulatory T-cells (Tregs) mediated by NSG myeloid APC. This enhanced suppressor activity was associated with higher levels of Treg GITR expression in the presence of NSG than NOD-scid APC. These collective results indicate NSG recipients might be efficiently employed to test the activity of T1D patient-derived ß-cell autoreactive T-cell clones and lines, but when screening for pathogenic effectors within polyclonal populations, Tregs should be removed from the transfer inoculum to avoid false negative results. PMID:26283479

  7. Maternal transfer of antibodies to the offspring after mice immunization with insect larvae-derived recombinant hepatitis E virus ORF-2 proteins.

    PubMed

    Jiménez de Oya, Nereida; Alonso-Padilla, Julio; Blázquez, Ana-Belén; Escribano-Romero, Estela; Escribano, José M; Saiz, Juan-Carlos

    2011-06-01

    Hepatitis E virus (HEV) is a major cause of acute hepatitis in humans, causing outbreaks and epidemics in regions with sub-optimal sanitary conditions, in many of which it is endemic. Nowadays there is no specific therapy or licensed vaccines against HEV infection. In this study, we have analyzed in mice the immunogenicity of HEV open-reading frame 2 (ORF-2) protein, and a truncated form of it lacking the first 111 amino acids, efficiently expressed in an improved baculovirus-based technology using insects as living biofactories. Both recombinant proteins elicited high and long-lasting specific anti HEV antibodies. Passive transfer of immunity from immunized mothers to their offspring was demonstrated to occur both by transplacental and lactation routes. These results indicate that these insect-derived immunogens constitute low-cost potential vaccine candidate to be further evaluated.

  8. Adoptive immunotherapy with genetically engineered T cells: modification of the IgG1 Fc 'spacer' domain in the extracellular moiety of chimeric antigen receptors avoids 'off-target' activation and unintended initiation of an innate immune response.

    PubMed

    Hombach, A; Hombach, A A; Abken, H

    2010-10-01

    Chimeric antigen receptors (CARs, immunoreceptors) are frequently used to redirect T cells with pre-defined specificity, in particular towards tumour cells for use in adoptive immunotherapy of malignant diseases. Specific targeting is mediated by an extracellularly located antibody-derived binding domain, which is joined to the transmembrane and intracellular CD3ζ moiety for T-cell activation. Stable CAR expression in T cells, however, requires a spacer domain interposed between the binding and the transmembrane domain and which is commonly the constant IgG1 Fc domain. We here revealed that CARs with Fc spacer domain bind to IgG Fc gamma receptors (FcγRs), thereby unintentionally activating innate immune cells, including monocytes and natural killer (NK) cells, which consequently secrete high amounts of pro-inflammatory cytokines. Engineered T cells, on the other hand, are likewise activated by FcγR binding resulting in cytokine secretion and lysis of monocytes and NK cells independently of the redirected specificity. To reduce FcγR binding, we modified the spacer domain without affecting CAR expression and antigen binding. Engineered with the modified CAR, T cells are not activated in presence of FcγR(+) cells, thereby minimizing the risk of off-target activation while preserving their redirected targeting specificity.

  9. 14 CFR 221.160 - Adoption notice.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 4 2012-01-01 2012-01-01 false Adoption notice. 221.160 Section 221.160... REGULATIONS TARIFFS Adoption Publications Required To Show Change in Carrier's Name or Transfer of Operating Control § 221.160 Adoption notice. (a) When the name of a carrier is changed or when its operating...

  10. 14 CFR 221.160 - Adoption notice.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 4 2014-01-01 2014-01-01 false Adoption notice. 221.160 Section 221.160... REGULATIONS TARIFFS Adoption Publications Required To Show Change in Carrier's Name or Transfer of Operating Control § 221.160 Adoption notice. (a) When the name of a carrier is changed or when its operating...

  11. 14 CFR 221.160 - Adoption notice.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 4 2011-01-01 2011-01-01 false Adoption notice. 221.160 Section 221.160... REGULATIONS TARIFFS Adoption Publications Required To Show Change in Carrier's Name or Transfer of Operating Control § 221.160 Adoption notice. (a) When the name of a carrier is changed or when its operating...

  12. 14 CFR 221.160 - Adoption notice.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 4 2013-01-01 2013-01-01 false Adoption notice. 221.160 Section 221.160... REGULATIONS TARIFFS Adoption Publications Required To Show Change in Carrier's Name or Transfer of Operating Control § 221.160 Adoption notice. (a) When the name of a carrier is changed or when its operating...

  13. 14 CFR 221.160 - Adoption notice.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Adoption notice. 221.160 Section 221.160... REGULATIONS TARIFFS Adoption Publications Required To Show Change in Carrier's Name or Transfer of Operating Control § 221.160 Adoption notice. (a) When the name of a carrier is changed or when its operating...

  14. Strengthening Adoption Practice, Listening to Adoptive Families

    ERIC Educational Resources Information Center

    Atkinson, Anne; Gonet, Patricia

    2007-01-01

    In-depth interviews with 500 adoptive families who received postadoption services through Virginia's Adoptive Family Preservation (AFP) program paint a richly detailed picture of the challenges adoptive families face and what they need to sustain adoption for many years after finalization. Findings document the need for support in a variety of…

  15. Safety and persistence of adoptively transferred autologous CD19-targeted T cells in patients with relapsed or chemotherapy refractory B-cell leukemias

    PubMed Central

    Rivière, Isabelle; Park, Jae H.; Davila, Marco L.; Wang, Xiuyan; Stefanski, Jolanta; Taylor, Clare; Yeh, Raymond; Bartido, Shirley; Borquez-Ojeda, Oriana; Olszewska, Malgorzata; Bernal, Yvette; Pegram, Hollie; Przybylowski, Mark; Hollyman, Daniel; Usachenko, Yelena; Pirraglia, Domenick; Hosey, James; Santos, Elmer; Halton, Elizabeth; Maslak, Peter; Scheinberg, David; Jurcic, Joseph; Heaney, Mark; Heller, Glenn; Frattini, Mark; Sadelain, Michel

    2011-01-01

    We report the findings from the first 10 patients with chemotherapy-refractory chronic lymphocytic leukemia (CLL) or relapsed B-cell acute lymphoblastic leukemia (ALL) we have enrolled for treatment with autologous T cells modified to express 19-28z, a second-generation chimeric antigen (Ag) receptor specific to the B-cell lineage Ag CD19. Eight of the 9 treated patients tolerated 19-28z+ T-cell infusions well. Three of 4 evaluable patients with bulky CLL who received prior conditioning with cyclophosphamide exhibited either a significant reduction or a mixed response in lymphadenopathy without concomitant development of B-cell aplasia. In contrast, one patient with relapsed ALL who was treated in remission with a similar T-cell dose developed a predicted B-cell aplasia. The short-term persistence of infused T cells was enhanced by prior cyclophosphamide administration and inversely proportional to the peripheral blood tumor burden. Further analyses showed rapid trafficking of modified T cells to tumor and retained ex vivo cytotoxic potential of CD19-targeted T cells retrieved 8 days after infusion. We conclude that this adoptive T-cell approach is promising and more likely to show clinical benefit in the setting of prior conditioning chemotherapy and low tumor burden or minimal residual disease. These studies are registered at www.clinicaltrials.org as #NCT00466531 (CLL protocol) and #NCT01044069 (B-ALL protocol). PMID:21849486

  16. Canine Adenovirus Vectors for Lung-Directed Gene Transfer: Efficacy, Immune Response, and Duration of Transgene Expression Using Helper-Dependent Vectors†

    PubMed Central

    Keriel, Anne; René, Céline; Galer, Chad; Zabner, Joseph; Kremer, Eric J.

    2006-01-01

    A major hurdle to the successful clinical use of some viral vectors relates to the innate, adaptive, and memory immune responses that limit the efficiency and duration of transgene expression. Some of these drawbacks may be circumvented by using vectors derived from nonhuman viruses such as canine adenovirus type 2 (CAV-2). Here, we evaluated the potential of CAV-2 vectors for gene transfer to the respiratory tract. We found that CAV-2 transduction was efficient in vivo in the mouse respiratory tract, and ex vivo in well-differentiated human pulmonary epithelia. Notably, the in vivo and ex vivo efficiency was poorly inhibited by sera from mice immunized with a human adenovirus type 5 (HAd5, a ubiquitous human pathogen) vector or by human sera containing HAd5 neutralizing antibodies. Following intranasal instillation in mice, CAV-2 vectors also led to a lower level of inflammatory cytokine secretion and cellular infiltration compared to HAd5 vectors. Moreover, CAV-2 transduction efficiency was increased in vitro in human pulmonary cells and in vivo in the mouse respiratory tract by FK228, a histone deacetylase inhibitor. Finally, by using a helper-dependent CAV-2 vector, we increased the in vivo duration of transgene expression to at least 3 months in immunocompetent mice without immunosuppression. Our data suggest that CAV-2 vectors may be efficient and safe tools for long-term clinical gene transfer to the respiratory tract. PMID:16415025

  17. Transfer of Maternal Immune Cells by Breastfeeding: Maternal Cytotoxic T Lymphocytes Present in Breast Milk Localize in the Peyer’s Patches of the Nursed Infant

    PubMed Central

    Tang, May; Zumba, Osvaldo; Mehta, Hetali; Toma, Annmarie; Sant’Angelo, Derek; Laouar, Yasmina

    2016-01-01

    Despite our knowledge of the protective role of antibodies passed to infants through breast milk, our understanding of immunity transfer via maternal leukocytes is still limited. To emulate the immunological interface between the mother and her infant while breast-feeding, we used murine pups fostered after birth onto MHC-matched and MHC-mismatched dams. Overall, data revealed that: 1) Survival of breast milk leukocytes in suckling infants is possible, but not significant after the foster-nursing ceases; 2) Most breast milk lymphocytes establish themselves in specific areas of the intestine termed Peyer’s patches (PPs); 3) While most leukocytes in the milk bolus were myeloid cells, the majority of breast milk leukocytes localized to PPs were T lymphocytes, and cytotoxic T cells (CTLs) in particular; 4) These CTLs exhibit high levels of the gut-homing molecules α4β7 and CCR9, but a reduced expression of the systemic homing marker CD62L; 5) Under the same activation conditions, transferred CD8 T cells through breast milk have a superior capacity to produce potent cytolytic and inflammatory mediators when compared to those generated by the breastfed infant. It is therefore possible that maternal CTLs found in breast milk are directed to the PPs to compensate for the immature adaptive immune system of the infant in order to protect it against constant oral infectious risks during the postnatal phase. PMID:27285085

  18. Health status and risk factors associated with failure of passive transfer of immunity in newborn beef calves in Québec

    PubMed Central

    Filteau, Virginie; Bouchard, Émile; Fecteau, Gilles; Dutil, Lucie; DuTremblay, Denis

    2003-01-01

    Risk factors associated with failure of passive transfer of immunity (FPT) were evaluated among newborn beef calves in Québec. Physical examination was performed on calves born of a normal calving and blood samples were collected for determination of health status and measurement of serum concentration of immunoglobulin (Ig) G1. Of 225 calves, from 45 herds, 19 % showed FPT (serum IgG1 concentration < 10.0 g/L). Calves born in a stanchion-stall were more likely to show FPT (OR: 10.2). Calves bottle-fed colostrum were less at risk for FPT (OR: 0.06). Calf gender, month of birth, dam parity, and dam body condition score were not associated with FPT. No association was detected between FPT and health status. Special care should be given to calves born from cows in a stanchion-stall to ensure adequate colostrum intake. Failure of passive transfer of immunity should be considered with other risk factors when investigating morbidity. PMID:14664353

  19. Medical Issues in Adoption

    MedlinePlus

    ... to Know About Zika & Pregnancy Medical Issues in Adoption KidsHealth > For Parents > Medical Issues in Adoption Print ... or emotional abuse of the child continue Agency Adoptions If you adopt through an agency, you might ...

  20. The Use of Video in Knowledge Transfer of Teacher-Led Psychosocial Interventions: Feeling Competent to Adopt a Different Role in the Classroom (L'utilisation de la vidéo dans le transfert de connaissances dans les interventions psychosociales menées par les enseignants : sentir que l'on a la compétence d'adopter un rôle différent dans la salle de classe)

    ERIC Educational Resources Information Center

    Beauregard, Caroline; Rousseau, Cécile; Mustafa, Sally

    2015-01-01

    Because they propose a form of modeling, videos have been recognised to be useful to transfer knowledge about practices requiring teachers to adopt a different role. This paper describes the results of a satisfaction survey with 98 teachers, school administrators and professionals regarding their appreciation of training videos showing teacher-led…

  1. Adoptive T-cell therapy for cancer: The era of engineered T cells.

    PubMed

    Bonini, Chiara; Mondino, Anna

    2015-09-01

    Tumors originate from a number of genetic events that deregulate homeostatic mechanisms controlling normal cell behavior. The immune system, devoted to patrol the organism against pathogenic events, can identify transformed cells, and in several cases cause their elimination. It is however clear that several mechanisms encompassing both central and peripheral tolerance limit antitumor immunity, often resulting into progressive diseases. Adoptive T-cell therapy with either allogeneic or autologous T cells can transfer therapeutic immunity. To date, genetic engineering of T cells appears to be a powerful tool for shaping tumor immunity. In this review, we discuss the most recent achievements in the areas of suicide gene therapy, and TCR-modified T cells and chimeric antigen receptor gene-modified T cells. We provide an overview of current strategies aimed at improving the safety and efficacy of these approaches, with an outlook on prospective developments.

  2. Adoptive immunotherapy combined with intratumoral TLR agonist delivery eradicates established melanoma in mice

    PubMed Central

    Amos, Sally M.; Pegram, Hollie J.; Westwood, Jennifer A.; John, Liza B.; Devaud, Christel; Clarke, Chris J.; Restifo, Nicholas P.; Smyth, Mark J.; Darcy, Phillip K.; Kershaw, Michael H.

    2012-01-01

    Toll-like receptor (TLR) agonists can trigger broad inflammatory responses that elicit rapid innate immunity and promote the activities of lymphocytes, which can potentially enhance adoptive immunotherapy in the tumor-bearing setting. In the present study, we found that Polyinosinic:Polycytidylic Acid [Poly(I:C)] and CpG oligodeoxynucleotide 1826 [CpG], agonists for TLR 3 and 9, respectively, potently activated adoptively transferred T cells against a murine model of established melanoma. Intratumoral injection of Poly(I:C) and CpG, combined with systemic transfer of activated pmel-1 T cells, specific for gp10025–33, led to enhanced survival and eradication of 9-day established subcutaneous B16F10 melanomas in a proportion of mice. A series of survival studies in knockout mice supported a key mechanistic pathway, whereby TLR agonists acted via host cells to enhance IFN-γ production by adoptively transferred T cells. IFN-γ, in turn, enhanced the immunogenicity of the B16F10 melanoma line, leading to increased killing by adoptively transferred T cells. Thus, this combination approach counteracted tumor escape from immunotherapy via downregulation of immunogenicity. In conclusion, TLR agonists may represent advanced adjuvants within the setting of adoptive T-cell immunotherapy of cancer and hold promise as a safe means of enhancing this approach within the clinic. PMID:21327636

  3. Enhancing B- and T-Cell Immune Response to a Hepatitis C Virus E2 DNA Vaccine by Intramuscular Electrical Gene Transfer

    PubMed Central

    Zucchelli, Silvia; Capone, Stefania; Fattori, Elena; Folgori, Antonella; Di Marco, Annalise; Casimiro, Danilo; Simon, Adam J.; Laufer, Ralph; La Monica, Nicola; Cortese, Riccardo; Nicosia, Alfredo

    2000-01-01

    We describe an improved genetic immunization strategy for eliciting a full spectrum of anti-hepatitis C virus (HCV) envelope 2 (E2) glycoprotein responses in mammals through electrical gene transfer (EGT) of plasmid DNA into muscle fibers. Intramuscular injection of a plasmid encoding a cross-reactive hypervariable region 1 (HVR1) peptide mimic fused at the N terminus of the E2 ectodomain, followed by electrical stimulation treatment in the form of high-frequency, low-voltage electric pulses, induced more than 10-fold-higher expression levels in the transfected mouse tissue. As a result of this substantial increment of in vivo antigen production, the humoral response induced in mice, rats, and rabbits ranged from 10- to 30-fold higher than that induced by conventional naked DNA immunization. Consequently, immune sera from EGT-treated mice displayed a broader cross-reactivity against HVR1 variants from natural isolates than sera from injected animals that were not subjected to electrical stimulation. Cellular response against E2 epitopes specific for helper and cytotoxic T cells was significantly improved by EGT. The EGT-mediated enhancement of humoral and cellular immunity is antigen independent, since comparable increases in antibody response against ciliary neurotrophic factor or in specific anti-human immunodeficiency virus type 1 gag CD8+ T cells were obtained in rats and mice. Thus, the method described potentially provides a safe, low-cost treatment that may be scaled up to humans and may hold the key for future development of prophylactic or therapeutic vaccines against HCV and other infectious diseases. PMID:11090158

  4. Dendritic cells and immunity against cancer

    PubMed Central

    Palucka, Karolina; Ueno, Hideki; Fay, Joseph; Banchereau, Jacques

    2010-01-01

    SUMMARY T cells can reject established tumors when adoptively transferred into patients, thereby demonstrating the power of the immune system for cancer therapy. However, it has proven difficult to maintain adoptively transferred T cells in the long term. Vaccines have the potential to induce tumor-specific effector and memory T cells. However, clinical efficacy of current vaccines is limited, possibly because tumors skew the immune system by means of myeloid-derived suppressor cells, inflammatory type 2 T cells and regulatory T cells (Tregs), all of which prevent the generation of effector cells. To improve the clinical efficacy of cancer vaccines in patients with metastatic disease, we need to design novel and improved strategies that can boost adaptive immunity to cancer, help overcome Tregs and allow the breakdown of the immunosuppressive tumor microenvironment. This can be achieved by exploiting the fast increasing knowledge about the dendritic cell (DC) system, including the existence of distinct DC subsets which respond differentially to distinct activation signals, (functional plasticity), both contributing to the generation of unique adaptive immune responses. We foresee that these novel cancer vaccines will be used as monotherapy in patients with resected disease, and in combination with drugs targeting regulatory/suppressor pathways in patients with metastatic disease. PMID:21158979

  5. Interleukin-2 gene transfer into murine neuroblastoma decreases tumorigenicity and enhances systemic immunity causing regression of preestablished retroperitoneal tumors.

    PubMed

    Katsanis, E; Orchard, P J; Bausero, M A; Gorden, K B; McIvor, R S; Blazar, B R

    1994-02-01

    Murine neuroblastoma, neuro-2a, was transduced with the retroviral vector LIL-2SN in order to examine the influence of localized interleukin (IL)-2 production on the immune response against a low major histocompatibility complex (MHC) class I, class II-negative, and intercellular adhesion molecule (ICAM)-1-negative tumor. Two neomycin-resistant (neo R) clones, N-2a/IL-2/L (2.5 +/- 0.4 U/ml/10(6) cells/24 h) and N-2a/IL-2/H (44.6 +/- 8.8 U/ml), were studied as representative low and high IL-2 producers, respectively. Using a recently developed retroperitoneal (r.p.) model for implantation of neuroblastoma in its natural site, we demonstrated that production of IL-2 by neuro-2a reduces its tumorigenicity in a dose-dependent fashion. T-cell, but not natural killer (NK) cell, depletion significantly increased tumor induced mortality in syngeneic A/J mice. Mice genetically devoid of T-cells (C.B-17 scid/scid) also experienced a significant increase in mortality rates. This indicates that the antitumor effect of locally secreted IL-2 is mediated primarily through activation of T-cells. Immunization of mice with irradiated N-2a/IL-2/H cells resulted in protection when challenged at a later date with unmodified neuro-2a cells. Depletion of CD8+, but not CD4+, T-cells prior to vaccination abrogated the protective effect, indicating that the priming phase of the immune response is CD8+ T-cell dependent. Mice with established r.p. tumors were vaccinated with N-2a/IL-2/H, which significantly prolonged their survival compared to unimmunized controls and to mice immunized with non-IL-2-producing neuro-2a cells. Because of the similarities of this model with the human tumor, our studies indicate that IL-2-transduced neuroblastoma cells may be effective in generating systemic immunity leading to eradication of minimal residual disease.

  6. Immune response

    MedlinePlus

    Innate immunity; Humoral immunity; Cellular immunity; Immunity; Inflammatory response; Acquired (adaptive) immunity ... and usually does not react against them. INNATE IMMUNITY Innate, or nonspecific, immunity is the defense system ...

  7. IL-2 / α-IL-2 Complex Treatment Cannot Be Substituted for the Adoptive Transfer of Regulatory T cells to Promote Bone Marrow Engraftment

    PubMed Central

    Mahr, Benedikt; Unger, Lukas; Hock, Karin; Pilat, Nina; Baranyi, Ulrike; Schwarz, Christoph; Maschke, Svenja; Farkas, Andreas Michael; Wekerle, Thomas

    2016-01-01

    Cell therapy with recipient Tregs achieves engraftment of allogeneic bone marrow (BM) without the need for cytoreductive conditioning (i.e., without irradiation or cytotoxic drugs). Thereby mixed chimerism and transplantation tolerance are established in recipients conditioned solely with costimulation blockade and rapamycin. However, clinical translation would be substantially facilitated if Treg-stimulating pharmaceutical agents could be used instead of individualized cell therapy. Recently, it was shown that interleukin-2 (IL-2) complexed with a monoclonal antibody (mAb) (clone JES6-1A12) against IL-2 (IL-2 complexes) potently expands and activates Tregs in vivo. Therefore, we investigated whether IL-2 complexes can replace Treg therapy in a costimulation blockade-based and irradiation-free BM transplantation (BMT) model. Unexpectedly, the administration of IL-2 complexes at the time of BMT (instead of Tregs) failed to induce BM engraftment in non-irradiated recipients (0/6 with IL-2 complexes vs. 3/4 with Tregs, p<0.05). Adding IL-2 complexes to an otherwise effective regimen involving recipient irradiation (1Gy) but no Treg transfer indeed actively triggered donor BM rejection at higher doses (0/8 with IL-2 complexes vs. 9/11 without, p<0.01) and had no detectable effect at two lower doses (3/5 vs. 9/11, p>0.05). CD8 T cells and NK cells of IL-2 complex-treated naïve mice showed an enhanced proliferative response towards donor antigens in vitro despite the marked expansion of Tregs. However, IL-2 complexes also expanded conventional CD4 T cells, CD8 T cells, NK cells, NKT cells and notably even B cells, albeit to a lesser extent. Notably, IL-2 complex expanded Tregs featured less potent suppressive functions than in vitro activated Tregs in terms of T cell suppression in vitro and BM engraftment in vivo. In conclusion, these data suggest that IL-2 complexes are less effective than recipient Tregs in promoting BM engraftment and in contrast actually trigger BM

  8. IL-2/α-IL-2 Complex Treatment Cannot Be Substituted for the Adoptive Transfer of Regulatory T cells to Promote Bone Marrow Engraftment.

    PubMed

    Mahr, Benedikt; Unger, Lukas; Hock, Karin; Pilat, Nina; Baranyi, Ulrike; Schwarz, Christoph; Maschke, Svenja; Farkas, Andreas Michael; Wekerle, Thomas

    2016-01-01

    Cell therapy with recipient Tregs achieves engraftment of allogeneic bone marrow (BM) without the need for cytoreductive conditioning (i.e., without irradiation or cytotoxic drugs). Thereby mixed chimerism and transplantation tolerance are established in recipients conditioned solely with costimulation blockade and rapamycin. However, clinical translation would be substantially facilitated if Treg-stimulating pharmaceutical agents could be used instead of individualized cell therapy. Recently, it was shown that interleukin-2 (IL-2) complexed with a monoclonal antibody (mAb) (clone JES6-1A12) against IL-2 (IL-2 complexes) potently expands and activates Tregs in vivo. Therefore, we investigated whether IL-2 complexes can replace Treg therapy in a costimulation blockade-based and irradiation-free BM transplantation (BMT) model. Unexpectedly, the administration of IL-2 complexes at the time of BMT (instead of Tregs) failed to induce BM engraftment in non-irradiated recipients (0/6 with IL-2 complexes vs. 3/4 with Tregs, p<0.05). Adding IL-2 complexes to an otherwise effective regimen involving recipient irradiation (1Gy) but no Treg transfer indeed actively triggered donor BM rejection at higher doses (0/8 with IL-2 complexes vs. 9/11 without, p<0.01) and had no detectable effect at two lower doses (3/5 vs. 9/11, p>0.05). CD8 T cells and NK cells of IL-2 complex-treated naïve mice showed an enhanced proliferative response towards donor antigens in vitro despite the marked expansion of Tregs. However, IL-2 complexes also expanded conventional CD4 T cells, CD8 T cells, NK cells, NKT cells and notably even B cells, albeit to a lesser extent. Notably, IL-2 complex expanded Tregs featured less potent suppressive functions than in vitro activated Tregs in terms of T cell suppression in vitro and BM engraftment in vivo. In conclusion, these data suggest that IL-2 complexes are less effective than recipient Tregs in promoting BM engraftment and in contrast actually trigger BM

  9. CMV-Specific CD8 T Cell Differentiation and Localization: Implications for Adoptive Therapies

    PubMed Central

    Smith, Corinne J.; Quinn, Michael; Snyder, Christopher M.

    2016-01-01

    Human cytomegalovirus (HCMV) is a ubiquitous virus that causes chronic infection and, thus, is one of the most common infectious complications of immune suppression. Adoptive transfer of HCMV-specific T cells has emerged as an effective method to reduce the risk for HCMV infection and/or reactivation by restoring immunity in transplant recipients. However, the CMV-specific CD8+ T cell response is comprised of a heterogenous mixture of subsets with distinct functions and localization, and it is not clear if current adoptive immunotherapy protocols can reconstitute the full spectrum of CD8+ T cell immunity. The aim of this review is to briefly summarize the role of these T cell subsets in CMV immunity and to describe how current adoptive immunotherapy practices might affect their reconstitution in patients. The bulk of the CMV-specific CD8+ T cell population is made up of terminally differentiated effector T cells with immediate effector function and a short life span. Self-renewing memory T cells within the CMV-specific population retain the capacity to expand and differentiate upon challenge and are important for the long-term persistence of the CD8+ T cell response. Finally, mucosal organs, which are frequent sites of CMV reactivation, are primarily inhabited by tissue-resident memory T cells, which do not recirculate. Future work on adoptive transfer strategies may need to focus on striking a balance between the formation of these subsets to ensure the development of long lasting and protective immune responses that can access the organs affected by CMV disease. PMID:27695453

  10. CMV-Specific CD8 T Cell Differentiation and Localization: Implications for Adoptive Therapies

    PubMed Central

    Smith, Corinne J.; Quinn, Michael; Snyder, Christopher M.

    2016-01-01

    Human cytomegalovirus (HCMV) is a ubiquitous virus that causes chronic infection and, thus, is one of the most common infectious complications of immune suppression. Adoptive transfer of HCMV-specific T cells has emerged as an effective method to reduce the risk for HCMV infection and/or reactivation by restoring immunity in transplant recipients. However, the CMV-specific CD8+ T cell response is comprised of a heterogenous mixture of subsets with distinct functions and localization, and it is not clear if current adoptive immunotherapy protocols can reconstitute the full spectrum of CD8+ T cell immunity. The aim of this review is to briefly summarize the role of these T cell subsets in CMV immunity and to describe how current adoptive immunotherapy practices might affect their reconstitution in patients. The bulk of the CMV-specific CD8+ T cell population is made up of terminally differentiated effector T cells with immediate effector function and a short life span. Self-renewing memory T cells within the CMV-specific population retain the capacity to expand and differentiate upon challenge and are important for the long-term persistence of the CD8+ T cell response. Finally, mucosal organs, which are frequent sites of CMV reactivation, are primarily inhabited by tissue-resident memory T cells, which do not recirculate. Future work on adoptive transfer strategies may need to focus on striking a balance between the formation of these subsets to ensure the development of long lasting and protective immune responses that can access the organs affected by CMV disease.

  11. The immune system in hypertension.

    PubMed

    Trott, Daniel W; Harrison, David G

    2014-03-01

    While hypertension has predominantly been attributed to perturbations of the vasculature, kidney, and central nervous system, research for almost 50 yr has shown that the immune system also contributes to this disease. Inflammatory cells accumulate in the kidneys and vasculature of humans and experimental animals with hypertension and likely contribute to end-organ damage. We and others have shown that mice lacking adaptive immune cells, including recombinase-activating gene-deficient mice and rats and mice with severe combined immunodeficiency have blunted hypertension to stimuli such as ANG II, high salt, and norepinephrine. Adoptive transfer of T cells restores the blood pressure response to these stimuli. Agonistic antibodies to the ANG II receptor, produced by B cells, contribute to hypertension in experimental models of preeclampsia. The central nervous system seems important in immune cell activation, because lesions in the anteroventral third ventricle block hypertension and T cell activation in response to ANG II. Likewise, genetic manipulation of reactive oxygen species in the subfornical organ modulates both hypertension and immune cell activation. Current evidence indicates that the production of cytokines, including tumor necrosis factor-α, interleukin-17, and interleukin-6, contribute to hypertension, likely via effects on both the kidney and vasculature. In addition, the innate immune system also appears to contribute to hypertension. We propose a working hypothesis linking the sympathetic nervous system, immune cells, production of cytokines, and, ultimately, vascular and renal dysfunction, leading to the augmentation of hypertension. Studies of immune cell activation will clearly be useful in understanding this common yet complex disease.

  12. Community Immunity (Herd Immunity)

    MedlinePlus

    ... Content Marketing Share this: Main Content Area ​Community Immunity ("Herd" Immunity) Vaccines can prevent outbreaks of disease and save ... disease is contained. This is known as "community immunity." In the illustration below, the top box depicts ...

  13. Neonatal Tetanus Immunity in Nigeria: The Effect of HIV Infection on Serum Levels and Transplacental Transfer of Antibodies.

    PubMed

    Bashir, Muhammad Faruk; Elechi, Hassan Abdullahi; Ashir, Mohammed Garba; Rabasa, Adamu Ibrahim; Bukbuk, David Nadeba; Usman, Ahmadu Baba; Mustapha, Modu Gofama; Alhaji, Mohammad Arab

    2016-01-01

    Background. Tetanus toxoid immunisation of pregnant mother has remained the most effective strategy in eliminating neonatal tetanus. Impaired production and/or transplacental transfer of antibodies may affect the effectiveness of this strategy. We studied the effect of maternal HIV infection on serum levels and transplacental transfer of anti-tetanus antibodies. Methods. A total of 162 mother-baby paired serum samples were taken and analysed for anti-tetanus antibody levels using ELISA. Maternal HIV status was also determined by double ELISA technique. Maternal TT vaccination status was also documented. Results. Thirty-eight (23.5%) mothers and 41 (25.3%) babies were seronegative, out of whom 8 mothers were HIV positive and 9 babies were HIV exposed. HIV infected mothers and HIV exposed infants were, respectively, 16.27 times (OR = 16.27, 95% CI = 3.28 to 80.61) and 33.75 times (OR = 33.75, 95% CI = 4.12 to 276.40) more likely to be seronegative for anti-tetanus antibody. Similarly, HIV positive mother-newborn pairs were 7.46 times more likely to have a poor transplacental transfer of tetanus antibodies (OR = 7.46, 95% CI = 1.96 to 28.41). Conclusions. Maternal HIV infection is associated with impaired maternofoetal transfer of anti-tetanus antibodies and seronegativity among mothers and their newborns. Hence, this may hinder efforts to eliminate neonatal tetanus. PMID:26904135

  14. Neonatal Tetanus Immunity in Nigeria: The Effect of HIV Infection on Serum Levels and Transplacental Transfer of Antibodies

    PubMed Central

    Ashir, Mohammed Garba; Rabasa, Adamu Ibrahim; Bukbuk, David Nadeba; Usman, Ahmadu Baba; Mustapha, Modu Gofama; Alhaji, Mohammad Arab

    2016-01-01

    Background. Tetanus toxoid immunisation of pregnant mother has remained the most effective strategy in eliminating neonatal tetanus. Impaired production and/or transplacental transfer of antibodies may affect the effectiveness of this strategy. We studied the effect of maternal HIV infection on serum levels and transplacental transfer of anti-tetanus antibodies. Methods. A total of 162 mother-baby paired serum samples were taken and analysed for anti-tetanus antibody levels using ELISA. Maternal HIV status was also determined by double ELISA technique. Maternal TT vaccination status was also documented. Results. Thirty-eight (23.5%) mothers and 41 (25.3%) babies were seronegative, out of whom 8 mothers were HIV positive and 9 babies were HIV exposed. HIV infected mothers and HIV exposed infants were, respectively, 16.27 times (OR = 16.27, 95% CI = 3.28 to 80.61) and 33.75 times (OR = 33.75, 95% CI = 4.12 to 276.40) more likely to be seronegative for anti-tetanus antibody. Similarly, HIV positive mother-newborn pairs were 7.46 times more likely to have a poor transplacental transfer of tetanus antibodies (OR = 7.46, 95% CI = 1.96 to 28.41). Conclusions. Maternal HIV infection is associated with impaired maternofoetal transfer of anti-tetanus antibodies and seronegativity among mothers and their newborns. Hence, this may hinder efforts to eliminate neonatal tetanus. PMID:26904135

  15. Formation of infectious dengue virus-antibody immune complex in vivo in marmosets (Callithrix jacchus) after passive transfer of anti-dengue virus monoclonal antibodies and infection with dengue virus.

    PubMed

    Moi, Meng Ling; Ami, Yasushi; Shirai, Kenji; Lim, Chang-Kweng; Suzaki, Yuriko; Saito, Yuka; Kitaura, Kazutaka; Saijo, Masayuki; Suzuki, Ryuji; Kurane, Ichiro; Takasaki, Tomohiko

    2015-02-01

    Infection with a dengue virus (DENV) serotype induces cross-reactive, weakly neutralizing antibodies to different dengue serotypes. It has been postulated that cross-reactive antibodies form a virus-antibody immune complex and enhance DENV infection of Fc gamma receptor (FcγR)-bearing cells. We determined whether infectious DENV-antibody immune complex is formed in vivo in marmosets after passive transfer of DENV-specific monoclonal antibody (mAb) and DENV inoculation and whether infectious DENV-antibody immune complex is detectable using FcγR-expressing cells. Marmosets showed that DENV-antibody immune complex was exclusively infectious to FcγR-expressing cells on days 2, 4, and 7 after passive transfer of each of the mAbs (mAb 4G2 and mAb 6B6C) and DENV inoculation. Although DENV-antibody immune complex was detected, contribution of the passively transferred antibody to overall viremia levels was limited in this study. The results indicate that DENV cross-reactive antibodies form DENV-antibody immune complex in vivo, which is infectious to FcγR-bearing cells but not FcγR-negative cells. PMID:25548383

  16. Induction of immunity to neuroblastoma early after syngeneic hematopoietic stem cell transplantation using a novel mouse tumor vaccine.

    PubMed

    Jing, Weiqing; Orentas, Rimas J; Johnson, Bryon D

    2007-03-01

    Autologous HSCT has resulted in improved event-free survival in patients with advanced neuroblastoma, but most of these patients still relapse. We previously reported that transient transfection of mouse neuroblastoma cells with plasmid DNA vectors encoding immune costimulatory molecules generates cell-based vaccines capable of inducing potent antitumor T cell immunity. In this study, we explored the effectiveness of tumor vaccine administration soon after HSCT. Soon after transplantation, only vaccinated mice that had received an adoptive transfer of syngeneic T cells survived tumor challenge. Tumor protective immunity in the transplant recipients was dependent on CD4(+) and CD8(+) T cells, and tumor-reactive T cells in the spleens of vaccinated mice could be detected in IFN-gamma enzyme-linked immunosorbent spot (ELISPOT) assays. Our data indicate that the adoptive transfer of T cells was absolutely required for induction of protective immunity by the tumor vaccine. Adoptive transfer of T cells accelerated T cell reconstitution, but it also resulted in increased percentages of CD4(+)CD25(+)Foxp3(+) cells soon after HSCT. Treatment of HSC transplant recipients with an anti-CD25 mAb before tumor vaccination inhibited antitumor immunity and significantly decreased the number of IFN-gamma-secreting tumor-specific CD4 T cells. However, physical depletion of CD25(+) cells from the adoptively transferred splenocytes appeared to increase the efficacy of tumor vaccination. Collectively, these results demonstrate that anti-neuroblastoma immunity can be induced soon after HSCT using a novel cell-based cancer vaccine. However, sufficient numbers of T cells must be added to the graft to achieve protective antitumor immunity, and depletion of CD25(+) T cells from adoptively transferred T cells might provide some additional benefit. These translational studies will aid in our development of post-HSCT vaccines for neuroblastoma.

  17. Comparison of passive transfer of immunity in neonatal dairy calves fed colostrum or bovine serum-based colostrum replacement and colostrum supplement products

    PubMed Central

    Poulsen, Keith P.; Foley, Andrea L.; Collins, Michael T.; McGuirk, Sheila M.

    2011-01-01

    Objective To compare serum total protein (sTP) and serum IgG (sIgG) concentrations in neonatal calves administered colostrum or a bovine serum-based colostrum replacement (CR) product followed by a bovine serum-based colostrum supplement (CS) product. Design Randomized controlled clinical trial. Animals 18 Jersey and 269 Holstein neonatal heifer calves. Procedures 141 calves were given 4 L of colostrum in 1 or 2 feedings (first or only feeding was provided ≤ 2 hours after birth; when applicable, a second feeding was provided between 2 and 12 hours after birth). Other calves (n = 146) were fed 2 L of a CR product ≤ 2 hours after birth and then 2 L of a CS product between 2 and 12 hours after birth. Concentrations of sTP and sIgG were measured 1 to 7 days after birth. Data from cohorts on individual farms and for all farms were analyzed. Results Mean sTP and sIgG concentrations differed significantly between feeding groups. In calves fed colostrum and calves fed CR and CS products, mean ± SD sTP concentration was 5.58 ± 0.67 g/dL and 5.26 ± 0.54 g/dL, respectively, and mean sIgG concentration was 1,868 ± 854 mg/dL and 1,320 ± 620 mg/dL, respectively. The percentage of calves that had failure of passive transfer of immunity (ie, sIgG concentrations < 1,000 mg/dL) was not significantly different between groups. Conclusions and Clinical Relevance Results suggested that sequential feeding of bovine serum-based CR and CS products to neonatal calves is an alternative to feeding colostrum for achieving passive transfer of immunity. PMID:20946083

  18. Adopted Children and Discipline

    MedlinePlus

    ... a Pediatrician Family Life Medical Home Family Dynamics Adoption & Foster Care Communication & Discipline Types of Families Media ... Your Community Healthy Children > Family Life > Family Dynamics > Adoption & Foster Care > Adopted Children & Discipline Family Life Listen ...

  19. Adoption & Foster Care

    MedlinePlus

    ... Children > Family Life > Family Dynamics > Adoption & Foster Care Adoption & Foster Care Article Body ​Each year, many children join families through adoption and foster care. These families may face unique ...

  20. Immune cell-mediated protection against vaginal candidiasis: evidence for a major role of vaginal CD4(+) T cells and possible participation of other local lymphocyte effectors.

    PubMed

    Santoni, Giorgio; Boccanera, Maria; Adriani, Daniela; Lucciarini, Roberta; Amantini, Consuelo; Morrone, Stefania; Cassone, Antonio; De Bernardis, Flavia

    2002-09-01

    The protective roles of different lymphocyte subsets were investigated in a rat vaginal candidiasis model by adoptive transfer of vaginal lymphocytes (VL) or sorted, purified CD3(+) T cells, CD4(+) or CD8(+) T cells, or CD3(-) CD5(+) B cells from the vaginas of naïve or immune rats following three rounds of Candida albicans infection. The adoptive transfer of total VL from nonimmune animals did not alter the course of vaginal candidiasis of the recipient rats. In contrast, the animals receiving total VL or CD3(+) T cells from immune rats showed a highly significant acceleration of fungus clearance compared with animals which received nonimmune VL. The animals with vaginal CD3(-) CD5(+) B cells transferred from immune rats also had fewer Candida CFU than the controls, but fungal clearance was significantly retarded with respect to the animals administered immune T cells. Sorted, purified CD4(+) and CD8(+) vaginal T cells from immune rats were also adoptively transferred to naïve animals. Although both populations were seen to accelerate the clearance of the fungus from the vagina, CD4(+) T cells were much more effective than CD8(+) T cells. Overall, there was no difference between the antifungal effects of immune vaginal CD4(+) T cells and those achievable with the transfer of whole, immune VL. Histological observations of the vaginal tissues of rats with adoptively transferred immune T cells demonstrated a remarkable accumulation of lymphocytes in the subepithelial lamina propria and also infiltrating the mucosal epithelium. These results strongly suggest that distinct vaginal lymphocyte subsets participate in the adaptive anti-Candida immunity at the vaginal level, with the vaginal CD4(+) T cells probably playing a major role.

  1. Differences in the effects of host suppression on the adoptive immunotherapy of subcutaneous and visceral tumors

    SciTech Connect

    Chang, A.E.; Shu, S.Y.; Chou, T.; Lafreniere, R.; Rosenberg, S.A.

    1986-07-01

    A syngeneic transplantable sarcoma induced in C57BL/6 mice, MCA 105, was used in studies to examine host suppression on the adoptive immunotherapy of established intradermal and experimentally induced pulmonary and hepatic metastases. Fresh immune splenocytes were generated from mice immunized to the MCA 105 tumor by a mixture of viable tumor cells and Corynebacterium parvum. The adoptive immunotherapy of intradermal MCA 105 tumor with immune cells required prior immunosuppression of the recipient by sublethal irradiation with 500 R or T-cell depletion. The effect of whole-body sublethal irradiation appeared to eliminate a systemic host suppression mechanism, since partialbody irradiation involving the tumor-bearing area did not permit successful immunotherapy. Host irradiation was not required to achieve successful immunotherapy of experimentally induced pulmonary or hepatic metastases. In nonirradiated recipients bearing both intradermal and pulmonary tumors, host suppression did not affect the function of transferred immune cells to induce regression of pulmonary metastases. Thus, suppression of adoptive immunotherapy appears to be relevant to tumors confined to the skin and subcutaneous tissue but not to tumor in visceral sites, such as the lung and liver.

  2. Accelerating immune reconstitution after hematopoietic stem cell transplantation

    PubMed Central

    Tzannou, Ifigeneia; Leen, Ann M

    2014-01-01

    Viral infections remain a significant cause of morbidity and mortality after hematopoietic stem cell transplantation. Pharmacologic agents are effective against some pathogens, but they are costly and can be associated with significant toxicities. Thus, many groups have investigated adoptive T-cell transfer as a means of hastening immune reconstitution and preventing and treating viral infections. This review discusses the immunotherapeutic strategies that have been explored. PMID:25505959

  3. The Family of Adoption.

    ERIC Educational Resources Information Center

    Pavao, Joyce Maguire

    This book aims to provide a broad framework within which to think about adoption as a whole system, so that everyone involved will learn to feel some empathy for the other members of the adoption process. The book, written by a family and adoption therapist who was adopted as an infant, describes predictable developmental stages and challenges for…

  4. Taking Adoption Seriously.

    ERIC Educational Resources Information Center

    Pierce, William

    1990-01-01

    Argues that adoption should be included in strategies to help children, teen parents, and other women with difficult pregnancies because adolescents are not equipped to raise children. Discusses the need for longitudinal research on adoption, adoption education in secondary schools, and studying mass media impact on adoption. (FMW)

  5. The immune system and cancer evasion strategies: therapeutic concepts.

    PubMed

    Muenst, S; Läubli, H; Soysal, S D; Zippelius, A; Tzankov, A; Hoeller, S

    2016-06-01

    The complicated interplay between cancer and the host immune system has been studied for decades. New insights into the human immune system as well as the mechanisms by which tumours evade immune control have led to the new and innovative therapeutic strategies that are considered amongst the medical breakthroughs of the last few years. Here, we will review the current understanding of cancer immunology in general, including immune surveillance and immunoediting, with a detailed look at immune cells (T cells, B cells, natural killer cells, macrophages and dendritic cells), immune checkpoints and regulators, sialic acid-binding immunoglobulin-like lectins (Siglecs) and other mechanisms. We will also present examples of new immune therapies able to reverse immune evasion strategies of tumour cells. Finally, we will focus on therapies that are already used in daily oncological practice such as the blockade of immune checkpoints cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed death-1 (PD-1) in patients with metastatic melanoma or advanced lung cancer, or therapies currently being tested in clinical trials such as adoptive T-cell transfer.

  6. SAP gene transfer restores cellular and humoral immune function in a murine model of X-linked lymphoproliferative disease.

    PubMed

    Rivat, Christine; Booth, Claire; Alonso-Ferrero, Maria; Blundell, Michael; Sebire, Neil J; Thrasher, Adrian J; Gaspar, H Bobby

    2013-02-14

    X-linked lymphoproliferative disease (XLP1) arises from mutations in the gene encoding SLAM-associated protein (SAP) and leads to abnormalities of NKT-cell development, NK-cell cytotoxicity, and T-dependent humoral function. Curative treatment is limited to allogeneic hematopoietic stem cell (HSC) transplantation. We tested whether HSC gene therapy could correct the multilineage defects seen in SAP(-/-) mice. SAP(-/-) murine HSCs were transduced with lentiviral vectors containing either SAP or reporter gene before transplantation into irradiated recipients. NKT-cell development was significantly higher and NK-cell cytotoxicity restored to wild-type levels in mice receiving the SAP vector in comparison to control mice. Baseline immunoglobulin levels were significantly increased and T-dependent humoral responses to NP-CGG, including germinal center formation, were restored in SAP-transduced mice.We demonstrate for the first time that HSC gene transfer corrects the cellular and humoral defects in SAP(-/-) mice providing proof of concept for gene therapy in XLP1.

  7. Protective cellular retroviral immunity requires both CD4+ and CD8+ immune T cells.

    PubMed Central

    Hom, R C; Finberg, R W; Mullaney, S; Ruprecht, R M

    1991-01-01

    We have found previously that postexposure chemoprophylaxis with 3'-azido-3'-deoxythymidine (also known as zidovudine or AZT) in combination with recombinant human alpha A/D interferon fully protected mice exposed to a lethal dose of Rauscher murine leukemia virus (RLV) against viremia and disease. After cessation of therapy, over 90% of these mice were able to resist rechallenge with live RLV, thus demonstrating an acquired immunity. Adoptive cell transfer of 4 x 10(7) cells from immunized mice fully protected naive recipients from viremia and splenomegaly after RLV challenge. However, when these immune T cells were fractionated into CD4+ and CD8+ subpopulations, only partial protection was found when 4 x 10(7) T cells of either subset were given. Full protection against RLV challenge was seen again when the T-cell subsets from immunized mice were recombined and transferred at the same number into naive mice. We conclude that cellular immunity alone is protective and that both CD4+ and CD8+ cell types are required for conferring full protection against live virus challenge. Images PMID:1898666

  8. Failure of Passive Immune Transfer in Calves: A Meta-Analysis on the Consequences and Assessment of the Economic Impact.

    PubMed

    Raboisson, Didier; Trillat, Pauline; Cahuzac, Clélia

    2016-01-01

    Low colostrum intake at birth results in the failure of passive transfer (FPT) due to the inadequate ingestion of colostral immunoglobulins (Ig). FPT is associated with an increased risk of mortality and decreased health and longevity. Despite the known management practices associated with low FPT, it remains an important issue in the field. Neither a quantitative analysis of FPT consequences nor an assessment of its total cost are available. To address this point, a meta-analysis on the adjusted associations between FPT and its outcomes was first performed. Then, the total costs of FPT in European systems were calculated using a stochastic method with adjusted values as the input parameters. The adjusted risks (and 95% confidence intervals) for mortality, bovine respiratory disease, diarrhoea and overall morbidity in the case of FPT were 2.12 (1.43-3.13), 1.75 (1.50-2.03), 1.51 (1.05-2.17) and 1.91 (1.63-2.24), respectively. The mean (and 95% prediction interval) total costs per calf with FPT were estimated to be €60 (€10-109) and €80 (€20-139) for dairy and beef, respectively. As a result of the double-step stochastic method, the proposed economic estimation constitutes the first estimate available for FPT. The results are presented in a way that facilitates their use in the field and, with limited effort, combines the cost of each contributor to increase the applicability of the economic assessment to the situations farm-advisors may face. The present economic estimates are also an important tool to evaluate the profitability of measures that aim to improve colostrum intake and FPT prevention. PMID:26986832

  9. Failure of Passive Immune Transfer in Calves: A Meta-Analysis on the Consequences and Assessment of the Economic Impact

    PubMed Central

    Raboisson, Didier; Trillat, Pauline; Cahuzac, Clélia

    2016-01-01

    Low colostrum intake at birth results in the failure of passive transfer (FPT) due to the inadequate ingestion of colostral immunoglobulins (Ig). FPT is associated with an increased risk of mortality and decreased health and longevity. Despite the known management practices associated with low FPT, it remains an important issue in the field. Neither a quantitative analysis of FPT consequences nor an assessment of its total cost are available. To address this point, a meta-analysis on the adjusted associations between FPT and its outcomes was first performed. Then, the total costs of FPT in European systems were calculated using a stochastic method with adjusted values as the input parameters. The adjusted risks (and 95% confidence intervals) for mortality, bovine respiratory disease, diarrhoea and overall morbidity in the case of FPT were 2.12 (1.43–3.13), 1.75 (1.50–2.03), 1.51 (1.05–2.17) and 1.91 (1.63–2.24), respectively. The mean (and 95% prediction interval) total costs per calf with FPT were estimated to be €60 (€10–109) and €80 (€20–139) for dairy and beef, respectively. As a result of the double-step stochastic method, the proposed economic estimation constitutes the first estimate available for FPT. The results are presented in a way that facilitates their use in the field and, with limited effort, combines the cost of each contributor to increase the applicability of the economic assessment to the situations farm-advisors may face. The present economic estimates are also an important tool to evaluate the profitability of measures that aim to improve colostrum intake and FPT prevention. PMID:26986832

  10. Failure of Passive Immune Transfer in Calves: A Meta-Analysis on the Consequences and Assessment of the Economic Impact.

    PubMed

    Raboisson, Didier; Trillat, Pauline; Cahuzac, Clélia

    2016-01-01

    Low colostrum intake at birth results in the failure of passive transfer (FPT) due to the inadequate ingestion of colostral immunoglobulins (Ig). FPT is associated with an increased risk of mortality and decreased health and longevity. Despite the known management practices associated with low FPT, it remains an important issue in the field. Neither a quantitative analysis of FPT consequences nor an assessment of its total cost are available. To address this point, a meta-analysis on the adjusted associations between FPT and its outcomes was first performed. Then, the total costs of FPT in European systems were calculated using a stochastic method with adjusted values as the input parameters. The adjusted risks (and 95% confidence intervals) for mortality, bovine respiratory disease, diarrhoea and overall morbidity in the case of FPT were 2.12 (1.43-3.13), 1.75 (1.50-2.03), 1.51 (1.05-2.17) and 1.91 (1.63-2.24), respectively. The mean (and 95% prediction interval) total costs per calf with FPT were estimated to be €60 (€10-109) and €80 (€20-139) for dairy and beef, respectively. As a result of the double-step stochastic method, the proposed economic estimation constitutes the first estimate available for FPT. The results are presented in a way that facilitates their use in the field and, with limited effort, combines the cost of each contributor to increase the applicability of the economic assessment to the situations farm-advisors may face. The present economic estimates are also an important tool to evaluate the profitability of measures that aim to improve colostrum intake and FPT prevention.

  11. Technological advances in adoptive immunotherapy.

    PubMed

    Oelke, Mathias; Krueger, Christine; Schneck, Jonathan P

    2005-01-01

    Adoptive immunotherapy is an attractive and elegant strategy for treating a variety of life-threatening diseases. Several approaches have been developed to generate antigen-specific CD4+ and CD8+ T cells for adoptive T-cell therapy in cancer and infectious diseases. Currently, many approaches are based on either the use of autologous peptide pulsed dendritic cells as antigen-presenting cells or nonspecific expansion of T cells. Unfortunately, current approaches lack the ability to serve as reproducible and economically viable methods. Several groups are developing new artificial approaches to overcome problems associated with dendritic cells and the nonspecific expansion of T-cell clones in order to make adoptive immunotherapy more feasible and effective. Thus, by increasing the availability of adoptive immunotherapy, we will be able to better determine the efficacy of the approaches in the treatment of a variety of diseases. In this review, we focus on technological advances that will facilitate adoptive immunotherapy. Specifically, we summarize current strategies which are either based on artificial antigen-presenting cells or on T-cell receptor gene transfer. PMID:15753966

  12. Questions about Adoption

    MedlinePlus

    ... Español Text Size Email Print Share Questions About Adoption Page Content Article Body What's the best way to handle my child's questions about her adoption? Many parents want to know when is the ...

  13. What's Happening in Adoption?

    ERIC Educational Resources Information Center

    Gallagher, Ursula M.

    1975-01-01

    Reviews current issues in adoption: termination of parental rights, rights of unwed fathers, subsidized adoption, the recent influx of Vietnamese children, black market babies, agency accountability in placing children, the right of the adoptee to know his biological parents. (ED)

  14. Adoption: The Bigger Boxes.

    ERIC Educational Resources Information Center

    Smyer, Michael A.

    1999-01-01

    Identifies two theoretical frameworks for adoption research: stress and coping literature and life-span developmental psychology. Recognizes that placing adoption within these larger study areas encourages differentiated, conditional questions such as when does adoption have which types of impacts for which types of individuals. (DLH)

  15. The Transracial Adoption Paradox

    PubMed Central

    Lee, Richard M.

    2008-01-01

    The number of transracial adoptions in the United States, particularly international adoptions, is increasing annually. Counseling psychology as a profession, however, is a relatively silent voice in the research on and practice of transracial adoption. This article presents an overview of the history and research on transracial adoption to inform counseling psychologists of the set of racial and ethnic challenges and opportunities that transracial adoptive families face in everyday living. Particular attention is given to emergent theory and research on the cultural socialization process within these families. PMID:18458794

  16. Split immunity: immune inhibition of rat gliomas by subcutaneous exposure to unmodified live tumor cells.

    PubMed

    Volovitz, Ilan; Marmor, Yotvat; Azulay, Meir; Machlenkin, Arthur; Goldberger, Ofir; Mor, Felix; Slavin, Shimon; Ram, Zvi; Cohen, Irun R; Eisenbach, Lea

    2011-11-15

    Gliomas that grow uninhibited in the brain almost never metastasize outside the CNS. The rare occurrences of extracranial metastasis are usually associated with a suppressed immune system. This observation raises the possibility that some gliomas might not grow outside the CNS due to an inherent immune response, We report in this study that the highly malignant F98 Fischer rat undifferentiated glioma, which grows aggressively in the brain, spontaneously regresses when injected live s.c. We found that this regression is immune-mediated and that it markedly enhances the survival or cures rats challenged with the same tumor intracranially either before or after the s.c. live-cell treatment. Adoptive transfer experiments showed the effect was immune-mediated and that the CD8 T cell fraction, which exhibited direct tumor cytotoxicity, was more effective than the CD4 T cell fraction in mediating resistance to intracranial challenge of naive rats. Brain tumors from treated rats exhibited enhanced CD3(+)CD8(+)CD4(-) and CD3(+)CD4(+)CD8(-) T cell infiltration and IFN-γ secretion. The results in the F98 glioma were corroborated in the Lewis rat CNS-1 astrocytoma. In both tumor models, s.c. treatment with live cells was significantly better than immunization with irradiated cells. We propose in this study a location-based immunotherapeutic phenomenon we term "split immunity": a tumor that thrives in an immune-privileged site may be inhibited by injecting live, unmodified tumor cells into a site that is not privileged, generating protective immunity that spreads back to the privileged site. Split immunity could explain several long-standing paradoxes regarding the lack of overt extracranial metastasis in patients with primary brain tumors.

  17. Immune System

    MedlinePlus

    ... How Can I Help a Friend Who Cuts? Immune System KidsHealth > For Teens > Immune System Print A A ... could put us out of commission. What the Immune System Does The immune (pronounced: ih-MYOON) system, which ...

  18. The claim from adoption.

    PubMed

    Petersen, Thomas Sobirk

    2002-08-01

    In this article several justifications of what I call 'the claim from adoption' are examined. The claim from adoption is that, instead of expending resources on bringing new children into the world using reproductive technology and then caring for these children, we ought to devote these resources to the adoption and care of existing destitute children. Arguments trading on the idea that resources should be directed to adoption instead of assisted reproduction because already existing people can benefit from such a use of resources whereas we cannot benefit individuals by bringing them into existence are rejected. It is then argued that a utilitarian argument proposed by Christian Munthe that supports the claim from adoption in some situations should be rejected because the support it offers does not extend to certain situations in which it seems morally obvious that resources should be expended on adoption rather than assisted reproduction. A version of the Priority View improves upon Munthe's utilitarianism by supporting the claim from adoption in the cases in which Munthe's argument failed. Some allegedly counterintuitive implications of the Priority View are then discussed, and it is concluded that the Priority View is more plausible than utilitarianism. In a concluding section on policy issues it is argued that, even though the claim from adoption can be justified in a variety of situations, it does not follow that, in these situations, governments should direct resources away from assisted reproduction and towards adoption.

  19. Adoptive cell therapy for sarcoma

    PubMed Central

    Mata, Melinda; Gottschalk, Stephen

    2015-01-01

    Current therapy for sarcomas, though effective in treating local disease, is often ineffective for patients with recurrent or metastatic disease. To improve outcomes, novel approaches are needed and cell therapy has the potential to meet this need since it does not rely on the cytotoxic mechanisms of conventional therapies. The recent successes of T-cell therapies for hematological malignancies have led to renewed interest in exploring cell therapies for solid tumors such as sarcomas. In this review, we will discuss current cell therapies for sarcoma with special emphasis on genetic approaches to improve the effector function of adoptively transferred cells. PMID:25572477

  20. Single Parent Adoption.

    ERIC Educational Resources Information Center

    Administration for Children, Youth, and Families (DHHS), Washington, DC.

    Presenting two views of the single-parent family, this pamphlet includes an article by two researchers (William Feigelman and Arnold R. Silverman) and a short statement by a single adoptive parent (Amanda Richards). The first paper summarizes earlier research on single-parent adoptions and discusses the results of a nationwide survey of 713…

  1. BET bromodomain inhibition enhances T cell persistence and function in adoptive immunotherapy models.

    PubMed

    Kagoya, Yuki; Nakatsugawa, Munehide; Yamashita, Yuki; Ochi, Toshiki; Guo, Tingxi; Anczurowski, Mark; Saso, Kayoko; Butler, Marcus O; Arrowsmith, Cheryl H; Hirano, Naoto

    2016-09-01

    Adoptive immunotherapy is a potentially curative therapeutic approach for patients with advanced cancer. However, the in vitro expansion of antitumor T cells prior to infusion inevitably incurs differentiation towards effector T cells and impairs persistence following adoptive transfer. Epigenetic profiles regulate gene expression of key transcription factors over the course of immune cell differentiation, proliferation, and function. Using comprehensive screening of chemical probes with defined epigenetic targets, we found that JQ1, an inhibitor of bromodomain and extra-terminal motif (BET) proteins, maintained CD8+ T cells with functional properties of stem cell-like and central memory T cells. Mechanistically, the BET protein BRD4 directly regulated expression of the transcription factor BATF in CD8+ T cells, which was associated with differentiation of T cells into an effector memory phenotype. JQ1-treated T cells showed enhanced persistence and antitumor effects in murine T cell receptor and chimeric antigen receptor gene therapy models. Furthermore, we found that histone acetyltransferase p300 supported the recruitment of BRD4 to the BATF promoter region, and p300 inhibition similarly augmented antitumor effects of the adoptively transferred T cells. These results demonstrate that targeting the BRD4-p300 signaling cascade supports the generation of superior antitumor T cell grafts for adoptive immunotherapy. PMID:27548527

  2. 14 CFR 221.162 - Receiver shall file adoption notices.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 4 2014-01-01 2014-01-01 false Receiver shall file adoption notices. 221... (AVIATION PROCEEDINGS) ECONOMIC REGULATIONS TARIFFS Adoption Publications Required To Show Change in Carrier's Name or Transfer of Operating Control § 221.162 Receiver shall file adoption notices. A...

  3. 14 CFR 221.162 - Receiver shall file adoption notices.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Receiver shall file adoption notices. 221... (AVIATION PROCEEDINGS) ECONOMIC REGULATIONS TARIFFS Adoption Publications Required To Show Change in Carrier's Name or Transfer of Operating Control § 221.162 Receiver shall file adoption notices. A...

  4. 14 CFR 221.162 - Receiver shall file adoption notices.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 4 2012-01-01 2012-01-01 false Receiver shall file adoption notices. 221... (AVIATION PROCEEDINGS) ECONOMIC REGULATIONS TARIFFS Adoption Publications Required To Show Change in Carrier's Name or Transfer of Operating Control § 221.162 Receiver shall file adoption notices. A...

  5. 14 CFR 221.162 - Receiver shall file adoption notices.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 4 2013-01-01 2013-01-01 false Receiver shall file adoption notices. 221... (AVIATION PROCEEDINGS) ECONOMIC REGULATIONS TARIFFS Adoption Publications Required To Show Change in Carrier's Name or Transfer of Operating Control § 221.162 Receiver shall file adoption notices. A...

  6. 14 CFR 221.162 - Receiver shall file adoption notices.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 4 2011-01-01 2011-01-01 false Receiver shall file adoption notices. 221... (AVIATION PROCEEDINGS) ECONOMIC REGULATIONS TARIFFS Adoption Publications Required To Show Change in Carrier's Name or Transfer of Operating Control § 221.162 Receiver shall file adoption notices. A...

  7. Usefulness of a commercial equine IgG test and serum protein concentration as indicators of failure of transfer of passive immunity in hospitalized foals.

    PubMed

    Metzger, Nadine; Hinchcliff, Kenneth W; Hardy, Joanne; Schwarzwald, Colin C; Wittum, Thomas

    2006-01-01

    Detection of failure of transfer of passive immunity (FTPI) is important in reducing morbidity and mortality in neonatal foals. We investigated the performance of a commercial equine IgG test (SNAP Foal IgG Test Kit) to diagnose FTPI in hospitalized foals. Furthermore, we evaluated the usefulness of serum total protein (STP) and serum globulin (SG) concentrations as indicators of FTPI. Serum IgG concentration was measured by means of the SNAP test and single radial immunodiffusion, and SG and STP concentrations were determined by means of a clinical chemistry analyzer. Subjects were 67 hospitalized foals <19 days old. The SNAP test was repeated on 37 samples from 29 foals, with identical results for 24 samples (kappa statistic, 0.64; 95% confidence interval [CI], 0.46-0.82). The sensitivity of the SNAP test to detect serum IgG concentration [IgG] < or =400 and < or =800 mg/dl was 90% (95% CI, 71-98%) and 95% (85-99%), respectively, and the specificity was 79% (71-82%) and 52% (39-57%), respectively. Sensitivity for detection of [IgG] < or =400 mg/dl was not affected (P > .05) by plasma fibrinogen concentration, sepsis score, or bacteremia. Specificity for detection of [IgG] < or = 800 mg/dl was lower (P < .05) in foals with sepsis score < or =11 (50% [31-60%] versus 100% [8-100%]) and bacteremia (25% [5-56%] versus 62% [45-62%]). Sensitivity and specificity of [STP] < or = 5.0 g/dl for [IgG] < or =800 mg/dl was 94% (83-99%) and 47% (30-56%), respectively. Performance of the SNAP test in hospitalized foals is impaired because of low specificity, but can have usefulness provided that the properties of the test and characteristics of the foal being examined are considered when interpreting the results. The STP and SG concentrations are poor sole indicators of FTPI in hospitalized foals, but may be useful adjunctive tests.

  8. The Colorado Adoption Project.

    PubMed

    Plomin, R; DeFries, J C

    1983-04-01

    This report provides an overview of the Colorado Adoption Project (CAP), a longitudinal, prospective, multivariate adoption study of behavioral development. Examples of the types of analyses that can be conducted using this design are presented. The examples are based on general cognitive-ability data for adoptive, biological, and control parents; assessments of their home environment; and Bayley Mental Development Index scores for 152 adopted children and 120 matched control children tested at both 1 and 2 years of age. The illustrative analyses include matched control children tested at both 1 and 2 years of age. The illustrative analyses include examination of genetic and environmental sources of variance, identification of environmental influence devoid of genetic bias, assessment of genotype-environment interaction and correlation, and analyses of the etiology of change and continuity in development.

  9. Adoption and Sibling Rivalry

    MedlinePlus

    ... child in your family should understand her own origins, and those of her brothers and sisters. But ... children can seem exaggerated because of their different origins. For instance, i f your adoptive child does ...

  10. Parenting Your Adopted Teenager

    MedlinePlus

    ... https: / / www. childwelfare. gov/ pubs/ f- openadopt/ .) The Internet and the explosion of social media sites (e. ... 4 Howard, J. (2012). Untangling the web: The Internet’s transformative impact on adoption . New York, NY: Evan ...

  11. Travelers' Health: International Adoption

    MedlinePlus

    ... preadoption living standards, varying disease epidemiology in the countries of origin, the presence of previously unidentified medical problems, and ... know the disease risks in the adopted child’s country of origin and the medical and social histories of the ...

  12. Lymph node trafficking of regulatory T cells is prerequisite for immune suppression.

    PubMed

    Huang, Miao-Tzu; Lin, Been-Ren; Liu, Wei-Liang; Lu, Chun-Wei; Chiang, Bor-Luen

    2016-04-01

    Regulatory T cells have a crucial role in health and disease because of their immune regulation function. However, the anatomic sites where regulatory T cells exert optimal immune regulation are open to debate. In our current study with the use of a shear-stress flow assay, we found that regulatory T cells exhibited significantly decreased adhesion to either activated endothelial monolayer or intercellular adhesion molecule 1 or E-selectin-coated surfaces compared with activated effector T cells. The less transmigration capacity of the regulatory T cells prompted our speculation of preferential lymph node localization for the regulatory T cells that endowed these cells with immune regulation function in the most efficient manner. To test this hypothesis, the role of lymph node localization in regulatory T cell-mediated immune suppression was evaluated with a footpad inflammation model. We found that adoptively transferred regulatory T cells inhibited the development of footpad inflammation. In addition, although blockage of CCR7 or CD62L had no effect on the immune suppressive function of the regulatory T cells per se, pretreatment of the regulatory T cells with either CCR7 or CD62L blocking antibodies prevented their recruitment into draining lymph nodes and concomitantly abrogated the immune suppressive effects of adoptively transferred regulatory T cells during footpad inflammation. Our data demonstrate the crucial role of lymph node localization in regulatory T cell-mediated immune suppression and suggest a probable hierarchy in the anatomic sites for optimal immune regulation. Elucidating the relationships between the transmigration characteristics of the regulatory T cells and their immune regulation function will provide insightful information for regulatory T cell-based cell therapy. PMID:26543091

  13. Protective immunity against recurrent Staphylococcus aureus skin infection requires antibody and interleukin-17A.

    PubMed

    Montgomery, Christopher P; Daniels, Melvin; Zhao, Fan; Alegre, Maria-Luisa; Chong, Anita S; Daum, Robert S

    2014-05-01

    Although many microbial infections elicit an adaptive immune response that can protect against reinfection, it is generally thought that Staphylococcus aureus infections fail to generate protective immunity despite detectable T and B cell responses. No vaccine is yet proven to prevent S. aureus infections in humans, and efforts to develop one have been hampered by a lack of animal models in which protective immunity occurs. Our results describe a novel mouse model of protective immunity against recurrent infection, in which S. aureus skin and soft tissue infection (SSTI) strongly protected against secondary SSTI in BALB/c mice but much less so in C57BL/6 mice. This protection was dependent on antibody, because adoptive transfer of immune BALB/c serum or purified antibody into either BALB/c or C57BL/6 mice resulted in smaller skin lesions. We also identified an antibody-independent mechanism, because B cell-deficient mice were partially protected against secondary S. aureus SSTI and adoptive transfer of T cells from immune BALB/c mice resulted in smaller lesions upon primary infection. Furthermore, neutralization of interleukin-17A (IL-17A) abolished T cell-mediated protection in BALB/c mice, whereas neutralization of gamma interferon (IFN-γ) enhanced protection in C57BL/6 mice. Therefore, protective immunity against recurrent S. aureus SSTI was advanced by antibody and the Th17/IL-17A pathway and prevented by the Th1/IFN-γ pathway, suggesting that targeting both cell-mediated and humoral immunity might optimally protect against secondary S. aureus SSTI. These findings also highlight the importance of the mouse genetic background in the development of protective immunity against S. aureus SSTI.

  14. Lymph node trafficking of regulatory T cells is prerequisite for immune suppression.

    PubMed

    Huang, Miao-Tzu; Lin, Been-Ren; Liu, Wei-Liang; Lu, Chun-Wei; Chiang, Bor-Luen

    2016-04-01

    Regulatory T cells have a crucial role in health and disease because of their immune regulation function. However, the anatomic sites where regulatory T cells exert optimal immune regulation are open to debate. In our current study with the use of a shear-stress flow assay, we found that regulatory T cells exhibited significantly decreased adhesion to either activated endothelial monolayer or intercellular adhesion molecule 1 or E-selectin-coated surfaces compared with activated effector T cells. The less transmigration capacity of the regulatory T cells prompted our speculation of preferential lymph node localization for the regulatory T cells that endowed these cells with immune regulation function in the most efficient manner. To test this hypothesis, the role of lymph node localization in regulatory T cell-mediated immune suppression was evaluated with a footpad inflammation model. We found that adoptively transferred regulatory T cells inhibited the development of footpad inflammation. In addition, although blockage of CCR7 or CD62L had no effect on the immune suppressive function of the regulatory T cells per se, pretreatment of the regulatory T cells with either CCR7 or CD62L blocking antibodies prevented their recruitment into draining lymph nodes and concomitantly abrogated the immune suppressive effects of adoptively transferred regulatory T cells during footpad inflammation. Our data demonstrate the crucial role of lymph node localization in regulatory T cell-mediated immune suppression and suggest a probable hierarchy in the anatomic sites for optimal immune regulation. Elucidating the relationships between the transmigration characteristics of the regulatory T cells and their immune regulation function will provide insightful information for regulatory T cell-based cell therapy.

  15. Immune response

    MedlinePlus

    ... cells. T cells are responsible for cell-mediated immunity. This type of immunity becomes deficient in persons with HIV, the virus ... blood. B lymphocytes provide the body with humoral immunity as they circulate in the fluids in search ...

  16. Immune Restoration

    MedlinePlus

    ... marrow cells immune to HIV infection. Letting the immune system repair itself: CD4 counts have increased for many ... have taken ART. Some scientists believe that the immune system might be able to heal and repair itself ...

  17. Immunometabolism: Cellular Metabolism Turns Immune Regulator.

    PubMed

    Loftus, Róisín M; Finlay, David K

    2016-01-01

    Immune cells are highly dynamic in terms of their growth, proliferation, and effector functions as they respond to immunological challenges. Different immune cells can adopt distinct metabolic configurations that allow the cell to balance its requirements for energy, molecular biosynthesis, and longevity. However, in addition to facilitating immune cell responses, it is now becoming clear that cellular metabolism has direct roles in regulating immune cell function. This review article describes the distinct metabolic signatures of key immune cells, explains how these metabolic setups facilitate immune function, and discusses the emerging evidence that intracellular metabolism has an integral role in controlling immune responses. PMID:26534957

  18. Adolescents' Feelings about Openness in Adoption: Implications for Adoption Agencies

    ERIC Educational Resources Information Center

    Berge, Jerica M.; Mendenhall, Tai J.; Wrobel, Gretchen M.; Grotevant, Harold D.; McRoy, Ruth G.

    2006-01-01

    Adoption research commonly uses parents' reports of satisfaction when examining openness in adoption arrangements. This qualitative study aimed to fill a gap in the adoption research by using adolescents' voices to gain a better understanding of their adoption experiences. Adopted adolescents (n = 152) were interviewed concerning their…

  19. Human class II major histocompatibility complex gene transfer into murine neuroblastoma leads to loss of tumorigenicity, immunity against subsequent tumor challenge, and elimination of microscopic preestablished tumors.

    PubMed

    Hock, R A; Reynolds, B D; Tucker-McClung, C L; Kwok, W W

    1995-01-01

    Immunological recognition of transformed cells is critically important to limit tumor development and proliferation. Because established tumors have escaped immune recognition and elimination, novel strategies to enhance antitumor immunity have been developed. A unique approach has used the introduction of genes encoding major histocompatibility complex (MHC) antigens into tumor cells. Experiments in mice have shown that the expression of syngeneic class II MHC antigens in tumor cells completely abrogates tumorigenicity and induces tumor-specific immunity. In this study we sought to determine whether a more effective antitumor immune response would be generated by introducing xenogeneic class II MHC genes into tumor cells. To address this question we used recombinant retroviruses to express human class II MHC genes in a highly malignant murine neuroblastoma cell line, Neuro-2a. We found that normal mice inoculated with Neuro-2a expressing the human class II MHC antigen did not develop tumors and were immune to subsequent challenge with unmodified Neuro-2a cells. In addition, mice bearing small established Neuro-2a tumors were cured by vaccination with Neuro-2a expressing human class II MHC. We hypothesize that a similar approach using retroviral-mediated transduction of class II MHC genes into human tumor cells may be an effective alternative to current cancer treatment.

  20. Vaccination of sheep against haemonchosis with H11, a gut membrane-derived protective antigen from the adult parasite: prevention of the periparturient rise and colostral transfer of protective immunity.

    PubMed

    Andrews, S J; Hole, N J; Munn, E A; Rolph, T P

    1995-07-01

    Pregnant ewes were immunised with a fraction highly enriched in the membrane glycoprotein antigen H11, isolated from the intestinal brush border of adult Haemonchus contortus. Immunity induced by immunisation was able to abolish almost completely (98-99%) the worm egg output from pregnant ewes challenged with ca. 10,000 infective larvae of H. contortus during the last trimester. Furthermore, lambs born and reared on vaccinated ewes had substantial antibody levels to H11 derived from maternal transfer. This antibody conferred moderate protection against a bolus challenge of ca. 3000 infective larvae of H. contortus in 5-week-old lambs.

  1. Autochthonous primary and metastatic melanomas in Hgf-Cdk4 R24C mice evade T-cell-mediated immune surveillance.

    PubMed

    Landsberg, Jennifer; Gaffal, Evelyn; Cron, Mira; Kohlmeyer, Judith; Renn, Marcel; Tüting, Thomas

    2010-10-01

    Genetically engineered mouse models offer new opportunities to investigate the role of cell-mediated immunity in the natural progression of melanoma in an immunocompetent host. Here we report that Hgf-Cdk4(R24C) mice spontaneously develop a spectrum of primary melanomas with high penetrance during their first year of life. Malignant transformation proceeds in a stepwise manner from multiple melanocytic nevi to single nodular melanomas and disseminated metastases in most mice. Migrating melanoma cells invade the draining lymph nodes without activating the immune system. Autochthonous primary tumors are destroyed following experimental introduction of immune surveillance using an adoptive lymphocyte transfer approach. However, some tumor cells are able to survive, evade immune cell control, and recur both locally and systemically. Immune tolerance in recurring tumors may be supported by immunosuppressive Gr1(+) myeloid cells. Taken together, our results demonstrate that primary and metastatic melanomas developing spontaneously in Hgf-Cdk4(R24C) mice effectively evade cellular immune surveillance.

  2. The Colorado Adoption Project.

    PubMed

    Rhea, Sally-Ann; Bricker, Josh B; Wadsworth, Sally J; Corley, Robin P

    2013-02-01

    This paper describes the Colorado Adoption Project (CAP), an ongoing genetically informative longitudinal study of behavioral development. We describe the features of the adoption design used in CAP, and discuss how this type of design uses data from both parent-offspring and related- versus unrelated-sibling comparisons to estimate the importance of genetic and shared environmental influences for resemblance among family members. The paper provides an overview of CAP's history, how subjects were ascertained, recruited, and retained, and the domains of assessment that have been explored since the CAP's initiation in 1975. Findings from some representative papers that make use of data from CAP participants illustrate the study's multifaceted nature as a parent-offspring and sibling behavioral genetic study, a study that parallels a complimentary twin study, a longitudinal study of development, a source of subjects for molecular genetic investigation, and a study of the outcomes of the adoption process itself. As subjects assessed first at age 1 approach age 40, we hope the CAP will establish itself as the first prospective adoption study of lifespan development.

  3. The Colorado Adoption Project

    PubMed Central

    Rhea, Sally-Ann; Bricker, Josh B.; Wadsworth, Sally J.; Corley, Robin P.

    2013-01-01

    This paper describes the Colorado Adoption Project (CAP), an ongoing genetically-informative longitudinal study of behavioral development. We describe the features of the adoption design used in CAP, and discuss how this type of design uses data from both parent-offspring and related- versus unrelated- sibling comparisons to estimate the importance of genetic and shared environmental influences for resemblance among family members. The paper provides an overview of CAP’s history, how subjects were ascertained, recruited, and retained, and the domains of assessment that have been explored since the CAP’s initiation in 1975. Findings from some representative papers that make use of data from CAP participants illustrate the study’s multifaceted nature as a parent-offspring and sibling behavioral genetic study, a study that parallels a complimentary twin study, a longitudinal study of development, a source of subjects for molecular genetic investigation, and a study of the outcomes of the adoption process itself. As subjects assessed first at age 1 approach age 40, we hope the CAP will establish itself as the first prospective adoption study of lifespan development. PMID:23158098

  4. CERTS customer adoption model

    SciTech Connect

    Rubio, F. Javier; Siddiqui, Afzal S.; Marnay, Chris; Hamachi,Kristina S.

    2000-03-01

    This effort represents a contribution to the wider distributed energy resources (DER) research of the Consortium for Electric Reliability Technology Solutions (CERTS, http://certs.lbl.gov) that is intended to attack and, hopefully, resolve the technical barriers to DER adoption, particularly those that are unlikely to be of high priority to individual equipment vendors. The longer term goal of the Berkeley Lab effort is to guide the wider technical research towards the key technical problems by forecasting some likely patterns of DER adoption. In sharp contrast to traditional electricity utility planning, this work takes a customer-centric approach and focuses on DER adoption decision making at, what we currently think of as, the customer level. This study reports on Berkeley Lab's second year effort (completed in Federal fiscal year 2000, FY00) of a project aimed to anticipate patterns of customer adoption of distributed energy resources (DER). Marnay, et al., 2000 describes the earlier FY99 Berkeley Lab work. The results presented herein are not intended to represent definitive economic analyses of possible DER projects by any means. The paucity of data available and the importance of excluded factors, such as environmental implications, are simply too important to make such an analysis possible at this time. Rather, the work presented represents a demonstration of the current model and an indicator of the potential to conduct more relevant studies in the future.

  5. Toddler Adoption: The Weaver's Craft.

    ERIC Educational Resources Information Center

    Hopkins-Best, Mary

    Based on concern about the lack of information on adopting toddlers, this book examines the special needs of adopted toddlers and their adoptive parents. Chapter 1, "Why Write a Book on Toddler Adoption?" details the lack of information on the difficulties of adopted toddlers in forming attachments and parents' child rearing difficulties. Chapter…

  6. Integrated Immune

    NASA Technical Reports Server (NTRS)

    Crucian, Brian; Mehta, Satish; Stowe, Raymond; Uchakin, Peter; Quiriarte, Heather; Pierson, Duane; Sams, Clarnece

    2010-01-01

    This slide presentation reviews the program to replace several recent studies about astronaut immune systems with one comprehensive study that will include in-flight sampling. The study will address lack of in-flight data to determine the inflight status of immune systems, physiological stress, viral immunity, to determine the clinical risk related to immune dysregulation for exploration class spaceflight, and to determine the appropriate monitoring strategy for spaceflight-associated immune dysfunction, that could be used for the evaluation of countermeasures.

  7. Open Adoption: Adoptive Parents' Reactions Two Decades Later

    ERIC Educational Resources Information Center

    Siegel, Deborah H.

    2013-01-01

    Unlike in the past, most adoption agencies today offer birth parents and adoptive parents the opportunity to share identifying information and have contact with each other. To understand the impacts of different open adoption arrangements, a qualitative descriptive study using a snowball sample of 44 adoptive parents throughout New England began…

  8. Hospitious Adoption: How Hospitality Empowers Children and Transforms Adoption

    ERIC Educational Resources Information Center

    Gritter, James L.

    2009-01-01

    Building on previous books by the author, "Hospitious Adoption: How Hospitality Empowers Children and Transforms Adoption" examines the next step after open adoption. Gritter takes the approach that practicing goodwill, respect, and courage within the realm of adoption makes the process move smoother and enriches children's lives. Following a…

  9. The Presence and Preferential Activation of Regulatory T Cells Diminish Adoptive Transfer of Autoimmune Diabetes by Polyclonal Nonobese Diabetic (NOD) T Cell Effectors into NSG versus NOD-scid Mice.

    PubMed

    Presa, Maximiliano; Chen, Yi-Guang; Grier, Alexandra E; Leiter, Edward H; Brehm, Michael A; Greiner, Dale L; Shultz, Leonard D; Serreze, David V

    2015-10-01

    NOD-scid.Il2rg(null) (NSG) mice are currently being used as recipients to screen for pathogenic autoreactive T cells in type 1 diabetes (T1D) patients. We questioned whether the restriction of IL-2R γ-chain (Il-2rγ)-dependent cytokine signaling only to donor cells in NSG recipients differently influenced the activities of transferred diabetogenic T cells when they were introduced as a monoclonal/oligoclonal population versus being part of a polyclonal repertoire. Unexpectedly, a significantly decreased T1D transfer by splenocytes from prediabetic NOD donors was observed in Il-2rγ(null)-NSG versus Il-2rγ-intact standard NOD-scid recipients. In contrast, NOD-derived monoclonal/oligoclonal TCR transgenic β cell-autoreactive T cells in either the CD8 (AI4, NY8.3) or CD4 (BDC2.5) compartments transferred disease significantly more rapidly to NSG than to NOD-scid recipients. The reduced diabetes transfer efficiency by polyclonal T cells in NSG recipients was associated with enhanced activation of regulatory T cells (Tregs) mediated by NSG myeloid APC. This enhanced suppressor activity was associated with higher levels of Treg GITR expression in the presence of NSG than NOD-scid APC. These collective results indicate NSG recipients might be efficiently employed to test the activity of T1D patient-derived β cell-autoreactive T cell clones and lines, but, when screening for pathogenic effectors within polyclonal populations, Tregs should be removed from the transfer inoculum to avoid false-negative results.

  10. More Evidence on the Impact of India's Conditional Cash Transfer Program, Janani Suraksha Yojana: Quasi-Experimental Evaluation of the Effects on Childhood Immunization and Other Reproductive and Child Health Outcomes

    PubMed Central

    Carvalho, Natalie; Thacker, Naveen; Gupta, Subodh S.; Salomon, Joshua A.

    2014-01-01

    Background In 2005, India established a conditional cash transfer program called Janani Suraksha Yojana (JSY), to increase institutional delivery and encourage the use of reproductive and child health-related services. Objective To assess the effect of maternal receipt of financial assistance from JSY on childhood immunizations, post-partum care, breastfeeding practices, and care-seeking behaviors. Methods We use data from the latest district-level household survey (2007–2008) to conduct a propensity score matching analysis with logistic regression. We conduct the analyses at the national level as well as separately across groups of states classified as high-focus and non-high-focus. We carry out several sensitivity analyses including a subgroup analysis stratified by possession of an immunization card. Results Receipt of financial assistance from JSY led to an increase in immunization rates ranging from 3.1 (95%CI 2.2–4.0) percentage points for one dose of polio vaccine to 9.1 (95%CI 7.5–10.7) percentage points in the proportion of fully vaccinated children. Our findings also indicate JSY led to increased post-partum check-up rates and healthy early breastfeeding practices around the time of childbirth. No effect of JSY was found on exclusive breastfeeding practices and care-seeking behaviors. Effect sizes were consistently larger in states identified as being a key focus for the program. In an analysis stratified by possession of an immunization card, there was little to no effect of JSY among those with vaccination cards, while the effect size was much larger than the base case results for those missing vaccination cards, across nearly all immunization outcomes. Conclusions Early results suggest the JSY program led to a significant increase in childhood immunization rates and some healthy reproductive health behaviors, but the structuring of financial incentives to pregnant women and health workers warrants further review. Causal interpretation of our

  11. Intra-amniotic rAAV-mediated microdystrophin gene transfer improves canine X-linked muscular dystrophy and may induce immune tolerance.

    PubMed

    Hayashita-Kinoh, Hiromi; Yugeta, Naoko; Okada, Hironori; Nitahara-Kasahara, Yuko; Chiyo, Tomoko; Okada, Takashi; Takeda, Shin'ichi

    2015-04-01

    Duchenne muscular dystrophy (DMD) is a severe congenital disease due to mutations in the dystrophin gene. Supplementation of dystrophin using recombinant adenoassociated virus vector has promise as a treatment of DMD, although therapeutic benefit of the truncated dystrophin still remains to be elucidated. Besides, host immune responses against the vector as well as transgene products have been denoted in the clinical gene therapy studies. Here, we transduced dystrophic dogs fetuses to investigate the therapeutic effects of an AAV vector expressing microdystrophin under conditions of immune tolerance. rAAV-CMV-microdystrophin and a rAAV-CAG-luciferase were injected into the amniotic fluid surrounding fetuses. We also reinjected rAAV9-CMV-microdystrophin into the jugular vein of an infant dystrophic dog to induce systemic expression of microdystrophin. Gait and cardiac function significantly improved in the rAAV-microdystrophin-injected dystrophic dog, suggesting that an adequate treatment of rAAV-microdystrophin with immune modulation induces successful long-term transgene expression to analyze improved dystrophic phenotype.

  12. Protection against 17D yellow fever encephalitis in mice by passive transfer of monoclonal antibodies to the nonstructural glycoprotein gp48 and by active immunization with gp48.

    PubMed

    Schlesinger, J J; Brandriss, M W; Walsh, E E

    1985-10-01

    The protective capacity of antiviral antibodies has generally been considered to depend on their interactions with structural components of the virion. Here we report protection against lethal 17D yellow fever virus (YF) encephalitis of mice by passive administration of nonneutralizing monoclonal antibodies to a 17D YF-specified nonstructural glycoprotein, gp48, and by active immunization with purified gp48. Among five anti-gp48 monoclonal antibodies tested, two with high titer complement-fixing (CF) activity were protective, whereas three antibodies with little or no CF activity were not. The ability of antibodies to protect correlated with their ability to promote complement-mediated cytolysis (CMC) of 51Cr-labeled 17D YF-infected mouse neuroblastoma (Neuro 2a) cells. Purified gp48, prepared from lysates of 17D YF-infected Vero cells by immunoaffinity chromatography, was shown to bear both YF type-specific and flavivirus group-reactive determinants in a solid phase radioimmunoassay. Immunization of mice with purified gp48 resulted in solid protection in the absence of detectable anti-virion antibody, measured by neutralization and radioimmunoprecipitation assays. The results are consistent with plasma membrane expression of gp48 and susceptibility of 17D YF-infected neural cells to CMC, a possible mechanism of host defense in 17D YF encephalitis. Protection provided by immunization with gp48, which bears a group-reactive determinant and is highly conserved among flaviviruses, may have implications in regard to flavivirus vaccine design.

  13. Intra-Amniotic rAAV-Mediated Microdystrophin Gene Transfer Improves Canine X-Linked Muscular Dystrophy and May Induce Immune Tolerance

    PubMed Central

    Hayashita-Kinoh, Hiromi; Yugeta, Naoko; Okada, Hironori; Nitahara-Kasahara, Yuko; Chiyo, Tomoko; Okada, Takashi; Takeda, Shin'ichi

    2015-01-01

    Duchenne muscular dystrophy (DMD) is a severe congenital disease due to mutations in the dystrophin gene. Supplementation of dystrophin using recombinant adenoassociated virus vector has promise as a treatment of DMD, although therapeutic benefit of the truncated dystrophin still remains to be elucidated. Besides, host immune responses against the vector as well as transgene products have been denoted in the clinical gene therapy studies. Here, we transduced dystrophic dogs fetuses to investigate the therapeutic effects of an AAV vector expressing microdystrophin under conditions of immune tolerance. rAAV-CMV-microdystrophin and a rAAV-CAG-luciferase were injected into the amniotic fluid surrounding fetuses. We also reinjected rAAV9-CMV-microdystrophin into the jugular vein of an infant dystrophic dog to induce systemic expression of microdystrophin. Gait and cardiac function significantly improved in the rAAV-microdystrophin-injected dystrophic dog, suggesting that an adequate treatment of rAAV-microdystrophin with immune modulation induces successful long-term transgene expression to analyze improved dystrophic phenotype. PMID:25586688

  14. Adoption Research: Trends, Topics, Outcomes

    ERIC Educational Resources Information Center

    Palacios, Jesus; Brodzinsky, David

    2010-01-01

    The current article provides a review of adoption research since its inception as a field of study. Three historical trends in adoption research are identified: the first focusing on risk in adoption and identifying adoptee-nonadoptee differences in adjustment; the second examining the capacity of adopted children to recover from early adversity;…

  15. ATM Technology Adoption in U.S. Campus Networking.

    ERIC Educational Resources Information Center

    Yao, Engui; Perry, John F.; Anderson, Larry S.; Brook, R. Dan; Hare, R. Dwight; Moore, Arnold J.; Xu, Xiaohe

    This study examined the relationships between ATM (asynchronous transfer mode) adoption in universities and four organizational variables: university size, type, finances, and information processing maturity. Another purpose of the study was to identify the current status of ATM adoption in campus networking. Subjects were university domain LAN…

  16. Childhood Immunization

    MedlinePlus

    ... lowest levels in history, thanks to years of immunization. Children must get at least some vaccines before ... child provide protection for many years, adults need immunizations too. Centers for Disease Control and Prevention

  17. Immunizations - diabetes

    MedlinePlus

    ... this page: //medlineplus.gov/ency/patientinstructions/000331.htm Immunizations - diabetes To use the sharing features on this page, please enable JavaScript. Immunizations (vaccines or vaccinations) help protect you from some ...

  18. Becoming Lesbian Adoptive Parents: An Exploratory Study of Lesbian Adoptive, Lesbian Birth, and Heterosexual Adoptive Parents.

    ERIC Educational Resources Information Center

    Shelley-Sireci, Lynn M.; Ciano-Boyce, Claudia

    2002-01-01

    Surveyed lesbian adoptive parents, heterosexual adoptive parents, and lesbian parents who had used assisted fertilization, regarding the adoption process. Found that the process was similar for both heterosexual and lesbian parents, but lesbian adoptive parents perceived more discrimination and were more inclined to omit information during the…

  19. Special topics in international adoption.

    PubMed

    Jenista, Jerri Ann

    2005-10-01

    As international adoption has become more "mainstream," the issues recently addressed in domestic adoption have become more important in adoptions involving children originating in other countries. Certain groups of prospective adoptive parents, such as gay or lesbian couples, single parents, and parents with disabilities, have begun to apply to adopt in ever increasing numbers. Children who may have been considered unadoptable in the past are now routinely being offered to prospective adoptive parents. The numbers and ages of the children placed and the spacing between adoptions have come under scrutiny. The rates of adoption dissolutions and disruptions are being examined carefully by the receiving and sending countries. There is a pressing need for research into numerous social aspects of adoption.

  20. Active Immunization with Extracellular Vesicles Derived from Staphylococcus aureus Effectively Protects against Staphylococcal Lung Infections, Mainly via Th1 Cell-Mediated Immunity.

    PubMed

    Choi, Seng Jin; Kim, Min-Hye; Jeon, Jinseong; Kim, Oh Youn; Choi, Youngwoo; Seo, Jihye; Hong, Sung-Wook; Lee, Won-Hee; Jeon, Seong Gyu; Gho, Yong Song; Jee, Young-Koo; Kim, Yoon-Keun

    2015-01-01

    Staphylococcus aureus is an important pathogenic bacterium that causes various infectious diseases. Extracellular vesicles (EVs) released from S. aureus contain bacterial proteins, nucleic acids, and lipids. These EVs can induce immune responses leading to similar symptoms as during staphylococcal infection condition and have the potential as vaccination agent. Here, we show that active immunization (vaccination) with S. aureus-derived EVs induce adaptive immunity of antibody and T cell responses. In addition, these EVs have the vaccine adjuvant ability to induce protective immunity such as the up-regulation of co-stimulatory molecules and the expression of T cell polarizing cytokines in antigen-presenting cells. Moreover, vaccination with S. aureus EVs conferred protection against lethality induced by airway challenge with lethal dose of S. aureus and also pneumonia induced by the administration of sub-lethal dose of S. aureus. These protective effects were also found in mice that were adoptively transferred with splenic T cells isolated from S. aureus EV-immunized mice, but not in serum transferred mice. Furthermore, this protective effect of S. aureus EVs was significantly reduced by the absence of interferon-gamma, but not by the absence of interleukin-17. Together, the study herein suggests that S. aureus EVs are a novel vaccine candidate against S. aureus infections, mainly via Th1 cellular response.

  1. The Relationships between Selected Organizational Variables and ATM Technology Adoption in Campus Networking.

    ERIC Educational Resources Information Center

    Yao, Engui

    1998-01-01

    Determines the relationships between ATM (Asynchronous Transfer Mode) adoption and four organizational variables: university size, type, finances, and information-processing maturity. Identifies the current status of ATM adoption in campus networking in the United States. Contains 33 references. (DDR)

  2. Echinoderm immunity.

    PubMed

    Smith, L Courtney; Ghosh, Julie; Buckley, Katherine M; Clow, Lori A; Dheilly, Nolwenn M; Haug, Tor; Henson, John H; Li, Chun; Lun, Cheng Man; Majeske, Audrey J; Matranga, Valeria; Nair, Sham V; Rast, Jonathan P; Raftos, David A; Roth, Mattias; Sacchi, Sandro; Schrankel, Catherine S; Stensvåg, Klara

    2010-01-01

    A survey for immune genes in the genome for the purple sea urchin has shown that the immune system is complex and sophisticated. By inference, immune responses of all echinoderms maybe similar. The immune system is mediated by several types of coelomocytes that are also useful as sensors of environmental stresses. There are a number of large gene families in the purple sea urchin genome that function in immunity and of which at least one appears to employ novel approaches for sequence diversification. Echinoderms have a simpler complement system, a large set of lectin genes and a number of antimicrobial peptides. Profiling the immune genes expressed by coelomocytes and the proteins in the coelomic fluid provide detailed information about immune functions in the sea urchin. The importance of echinoderms in maintaining marine ecosystem stability and the disastrous effects of their removal due to disease will require future collaborations between ecologists and immunologists working towards understanding and preserving marine habitats. PMID:21528703

  3. Parents' Feelings towards Their Adoptive and Non-Adoptive Children

    ERIC Educational Resources Information Center

    Glover, Marshaun B.; Mullineaux, Paula Y.; Deater-Deckard, Kirby; Petrill, Stephen A.

    2010-01-01

    In the current study, we examined parent gender differences in feelings (negativity and positivity) and perceptions of child behavioural and emotional problems in adoptive and biological parent-child dyads. In a sample of 85 families, we used a novel within-family adoption design in which one child was adopted and one child was a biological child…

  4. Open adoption: adoptive parents' reactions two decades later.

    PubMed

    Siegel, Deborah H

    2013-01-01

    Unlike in the past, most adoption agencies today offer birth parents and adoptive parents the opportunity to share identifying information and have contact with each other. To understand the impacts of different open adoption arrangements, a qualitative descriptive study using a snowball sample of 44 adoptive parents throughout New England began in 1988. Every seven years these parents who adopted infants in open adoptions have participated in tape-recorded interviews to explore their evolving reactions to their open adoption experiences. This article reports the results of in-depth interviews with these parents now that their children have reached young adulthood. This longitudinal research illuminates how open adoptions change over the course of childhood and adolescence, parents' feelings about open adoption, challenges that emerge in their relationships with their children's birth families, how those challenges are managed and viewed, and parents' advice for others living with open adoption and for clinical social work practice and policy. Findings reveal that regardless of the type of openness, these adoptive parents generally feel positive about knowing the birth parents and having contact with them, are comfortable with open adoption, and see it serving the child's best interests.

  5. Who Is Adopted? Measuring Adoption Status Using National Survey Data.

    ERIC Educational Resources Information Center

    Miller, Brent C.; Bayley, Bruce K.; Christensen, Mathew; Fan, Xitao; Coyl, Diana; Grotevant, Harold D.; van Dulmen, Manfred; Dunbar, Nora

    2001-01-01

    Draws on data from the National Longitudinal Survey of Adolescent Health to illustrate the complexities of using large-scale surveys to measure adoption status. Discusses conceptual and methodological issues in measuring adoption status. Presents decision rules for determining adoption status across three sources of data: school self-administered…

  6. MmuPV1 infection and tumor development of T cell-deficient mice is prevented by passively transferred hyperimmune sera from normal congenic mice immunized with MmuPV1 virus-like particles (VLPs).

    PubMed

    Joh, Joongho; Ghim, Shin-je; Chilton, Paula M; Sundberg, John P; Park, Jino; Wilcher, Sarah A; Proctor, Mary L; Bennett Jenson, A

    2016-02-01

    Infection by mouse papillomavirus (PV), MmuPV1, of T cell-deficient, B6.Cg-Foxn1(nu)/J nude mice revealed that four, distinct squamous papilloma phenotypes developed simultaneously after infection of experimental mice. Papillomas appeared on the muzzle, vagina, and tail at or about day 42days post-inoculation. The dorsal skin developed papillomas and hair follicle tumors (trichoblastomas) as early as 26days after infection. Passive transfer of hyperimmune sera from normal congenic mice immunized with MmuPV1 virus-like particles (VLPs) to T cell-deficient strains of mice prevented infection by virions of experimental mice. This study provides further evidence that T cell deficiency is critical for tumor formation by MmuPV1 infection. PMID:26778691

  7. Immune response to intrapharyngeal LPS in neonatal and juvenile mice.

    PubMed

    McGrath-Morrow, Sharon A; Lee, Seakwoo; Gibbs, Kevin; Lopez, Armando; Collaco, Joseph M; Neptune, Enid; Soloski, Mark J; Scott, Alan; D'Alessio, Franco

    2015-03-01

    Neonates and infants have a higher morbidity and mortality associated with lower respiratory tract illnesses compared with older children. To identify age-related and longitudinal differences in the cellular immune response to acute lung injury (ALI), neonatal and juvenile mice were given Escherichia coli LPS using a novel, minimally invasive aspiration technique. Neonatal and juvenile mice received between 3.75 and 7.5 mg/kg LPS by intrapharyngeal aspiration. Airway and lung cells were isolated and characterized by flow cytometry, cytokine/chemokine mRNA expression from lung homogenates was quantified, and lung morphometry and injury scores were performed. LPS-treated neonatal mice underwent adoptive transfer with adult T regulatory cells (Tregs). After LPS aspiration, lung monocytes isolated from neonatal mice had a predominant M2 phenotype, whereas lung monocytes from juvenile mice displayed a mixed M1/M2 phenotype. At 72 hours after LPS exposure, neonatal lungs were slower to resolve inflammation and expressed lower mRNA levels of CCL2, CCL5, CXCL10, and IL-10. Juvenile, but not neonatal, mice demonstrated a significant increase in airway Tregs after LPS exposure. Adoptive transfer of adult Tregs into LPS-challenged neonatal mice resulted in reduced lung inflammation and improved weight gain. These findings underscore several vulnerabilities in the neonatal immune response to LPS-induced ALI. Most striking was the deficiency in airway Tregs after LPS aspiration. Adoptive transfer of adult Tregs mitigated LPS-induced ALI in neonatal mice, highlighting the importance of age-related differences in Tregs and their response to ALI during early postnatal development.

  8. Cancer immunotherapy and breaking immune tolerance: new approaches to an old challenge.

    PubMed

    Makkouk, Amani; Weiner, George J

    2015-01-01

    Cancer immunotherapy has proven to be challenging as it depends on overcoming multiple mechanisms that mediate immune tolerance to self-antigens. A growing understanding of immune tolerance has been the foundation for new approaches to cancer immunotherapy. Adoptive transfer of immune effectors such as antitumor mAb and chimeric antigen receptor T cells bypasses many of the mechanisms involved in immune tolerance by allowing for expansion of tumor-specific effectors ex vivo. Vaccination with whole tumor cells, protein, peptide, or dendritic cells has proven challenging, yet may be more useful when combined with other cancer immunotherapeutic strategies. Immunomodulatory approaches to cancer immunotherapy include treatment with agents that enhance and maintain T-cell activation. Recent advances in the use of checkpoint blockade to block negative signals and to maintain the antitumor response are particularly exciting. With our growing knowledge of immune tolerance and ways to overcome it, combination treatments are being developed, tested, and have particular promise. One example is in situ immunization that is designed to break tolerance within the tumor microenvironment. Progress in all these areas is continuing based on clear evidence that cancer immunotherapy designed to overcome immune tolerance can be useful for a growing number of patients with cancer.

  9. Surfactant Protein-D Is Essential for Immunity to Helminth Infection.

    PubMed

    Thawer, Sumaiyya; Auret, Jennifer; Schnoeller, Corinna; Chetty, Alisha; Smith, Katherine; Darby, Matthew; Roberts, Luke; Mackay, Rosie-Marie; Whitwell, Harry J; Timms, John F; Madsen, Jens; Selkirk, Murray E; Brombacher, Frank; Clark, Howard William; Horsnell, William G C

    2016-02-01

    Pulmonary epithelial cell responses can enhance type 2 immunity and contribute to control of nematode infections. An important epithelial product is the collectin Surfactant Protein D (SP-D). We found that SP-D concentrations increased in the lung following Nippostrongylus brasiliensis infection; this increase was dependent on key components of the type 2 immune response. We carried out loss and gain of function studies of SP-D to establish if SP-D was required for optimal immunity to the parasite. N. brasiliensis infection of SP-D-/- mice resulted in profound impairment of host innate immunity and ability to resolve infection. Raising pulmonary SP-D levels prior to infection enhanced parasite expulsion and type 2 immune responses, including increased numbers of IL-13 producing type 2 innate lymphoid cells (ILC2), elevated expression of markers of alternative activation by alveolar macrophages (alvM) and increased production of the type 2 cytokines IL-4 and IL-13. Adoptive transfer of alvM from SP-D-treated parasite infected mice into naïve recipients enhanced immunity to N. brasiliensis. Protection was associated with selective binding by the SP-D carbohydrate recognition domain (CRD) to L4 parasites to enhance their killing by alvM. These findings are the first demonstration that the collectin SP-D is an essential component of host innate immunity to helminths. PMID:26900854

  10. Surfactant Protein-D Is Essential for Immunity to Helminth Infection.

    PubMed

    Thawer, Sumaiyya; Auret, Jennifer; Schnoeller, Corinna; Chetty, Alisha; Smith, Katherine; Darby, Matthew; Roberts, Luke; Mackay, Rosie-Marie; Whitwell, Harry J; Timms, John F; Madsen, Jens; Selkirk, Murray E; Brombacher, Frank; Clark, Howard William; Horsnell, William G C

    2016-02-01

    Pulmonary epithelial cell responses can enhance type 2 immunity and contribute to control of nematode infections. An important epithelial product is the collectin Surfactant Protein D (SP-D). We found that SP-D concentrations increased in the lung following Nippostrongylus brasiliensis infection; this increase was dependent on key components of the type 2 immune response. We carried out loss and gain of function studies of SP-D to establish if SP-D was required for optimal immunity to the parasite. N. brasiliensis infection of SP-D-/- mice resulted in profound impairment of host innate immunity and ability to resolve infection. Raising pulmonary SP-D levels prior to infection enhanced parasite expulsion and type 2 immune responses, including increased numbers of IL-13 producing type 2 innate lymphoid cells (ILC2), elevated expression of markers of alternative activation by alveolar macrophages (alvM) and increased production of the type 2 cytokines IL-4 and IL-13. Adoptive transfer of alvM from SP-D-treated parasite infected mice into naïve recipients enhanced immunity to N. brasiliensis. Protection was associated with selective binding by the SP-D carbohydrate recognition domain (CRD) to L4 parasites to enhance their killing by alvM. These findings are the first demonstration that the collectin SP-D is an essential component of host innate immunity to helminths.

  11. Surfactant Protein-D Is Essential for Immunity to Helminth Infection

    PubMed Central

    Schnoeller, Corinna; Chetty, Alisha; Smith, Katherine; Darby, Matthew; Roberts, Luke; Mackay, Rosie-Marie; Whitwell, Harry J.; Timms, John F.; Madsen, Jens; Selkirk, Murray E.; Brombacher, Frank; Clark, Howard William; Horsnell, William G. C.

    2016-01-01

    Pulmonary epithelial cell responses can enhance type 2 immunity and contribute to control of nematode infections. An important epithelial product is the collectin Surfactant Protein D (SP-D). We found that SP-D concentrations increased in the lung following Nippostrongylus brasiliensis infection; this increase was dependent on key components of the type 2 immune response. We carried out loss and gain of function studies of SP-D to establish if SP-D was required for optimal immunity to the parasite. N. brasiliensis infection of SP-D-/- mice resulted in profound impairment of host innate immunity and ability to resolve infection. Raising pulmonary SP-D levels prior to infection enhanced parasite expulsion and type 2 immune responses, including increased numbers of IL-13 producing type 2 innate lymphoid cells (ILC2), elevated expression of markers of alternative activation by alveolar macrophages (alvM) and increased production of the type 2 cytokines IL-4 and IL-13. Adoptive transfer of alvM from SP-D-treated parasite infected mice into naïve recipients enhanced immunity to N. brasiliensis. Protection was associated with selective binding by the SP-D carbohydrate recognition domain (CRD) to L4 parasites to enhance their killing by alvM. These findings are the first demonstration that the collectin SP-D is an essential component of host innate immunity to helminths. PMID:26900854

  12. Lymphocyte function associated antigen-1, integrin alpha 4, and L-selectin mediate T-cell homing to the pancreas in the model of adoptive transfer of diabetes in NOD mice.

    PubMed

    Fabien, N; Bergerot, I; Orgiazzi, J; Thivolet, C

    1996-09-01

    The involvement of adhesion molecule in the process of T-cell homing to the pancreas was investigated in the model of the T-cell transfer of type I diabetes in NOD mice. Treatment of mice using monoclonal anti-lymphocyte function associated antigen (LFA)-1, anti-integrin alpha 4, anti-intercellular adhesion molecule (ICAM)-1, and anti-L-selectin antibodies (monoclonal antibodies [mAbs]) gave rise to a partial or complete prevention of diabetes via different mechanisms of protection. On day 20 posttransfer, diabetes was only observed in control mice (26 of 32) and in few mice treated with the anti-L-selectin mAbs (3 of 24). On day 60, the best protection was observed using the anti-LFA-1 or the anti-integrin alpha 4 mAbs with 3 of 11 and 2 of 5 diabetic mice, respectively. On day 20, no insulitis was observed in the pancreases of mice treated with these mAbs compared with the pancreases of controls, suggesting that such treatment blocked the penetration of T-cells into the islets. In vitro adhesion assays confirmed that adhesion of T-cells to the pancreatic endothelium was blocked, except when using the anti-L-selectin mAb, which induced a modification of the traffic of the transferred T-cells; the ability of T-cells to migrate into the pancreatic lymph nodes was significantly reduced (10.4 vs. 22%). Anti-LFA-1 mAbs did not modify such T-cell trafficking. The present study, therefore, elucidates the role of LFA-1, integrin alpha 4, and L-selectin in T-cell homing to the pancreas, first step of the cascade of events leading to type I diabetes. PMID:8772719

  13. Alkylating agent melphalan augments the efficacy of adoptive immunotherapy using tumor-specific CD4+ T cells

    PubMed Central

    Lu, Xiaoyun; Ding, Zhi-Chun; Cao, Yang; Liu, Chufeng; Habtetsion, Tsadik; Yu, Miao; Lemos, Henrique; Salman, Huda; Xu, Hongyan; Mellor, Andrew L.; Zhou, Gang

    2014-01-01

    In recent years the immune-potentiating effects of some widely used chemotherapeutic agents have been increasingly appreciated. This provides a rationale for combining conventional chemotherapy with immunotherapy strategies to achieve durable therapeutic benefits. Previous studies have implicated the immunomodulatory effects of melphalan, an alkylating agent commonly used to treat multiple myeloma, but the underlying mechanisms remain obscure. In the current study, we investigated the impact of melphalan on endogenous immune cells as well as adoptively transferred tumor-specific CD4+ T cells in tumor-bearing mice. We showed that melphalan treatment resulted in a rapid burst of inflammatory cytokines and chemokines during the cellular recovery phase after melphalan-induced myelo-leukodepletion. After melphalan treatment, tumor cells exhibited characteristics of immunogenic cell death, including membrane translocation of the endoplasmic reticulum resident calreticulin (CRT), and extracellular release of high-mobility group box 1 (HMGB1). In addition, there was enhanced tumor antigen uptake by dendritic cells in the tumor-draining lymph node. Consistent with these immunomodulatory effects, melphalan treatment of tumor-bearing mice led to the activation of the endogenous CD8+ T cells, and more importantly, effectively drove the clonal expansion and effector differentiation of adoptively transferred tumor-specific CD4+ T cells. Notably, the combination of melphalan and CD4+ T-cell adoptive cell therapy (ACT) was more efficacious than either treatment alone in prolonging the survival of mice with advanced B-cell lymphomas or colorectal tumors. These findings provide mechanistic insights into melphalan’s immunostimulatory effects, and demonstrate the therapeutic potential of combining melphalan with adoptive cell therapy utilizing antitumor CD4+ T cells. PMID:25560408

  14. The Texas Adoption Project: adopted children and their intellectual resemblance to biological and adoptive parents.

    PubMed

    Horn, J M

    1983-04-01

    Intelligence test scores were obtained from parents and children in 300 adoptive families and compared with similar measures available for the biological mothers of the same adopted children. Results supported the hypothesis that genetic variability is an important influence in the development of individual differences for intelligence. The most salient finding was that adopted children resemble their biological mothers more than they resemble the adoptive parents who reared them from birth. A small subset of the oldest adopted children did not resemble their biological mothers. The suggestion that the influence of genes declines with age is treated with caution since other adoption studies report a trend in the opposite direction.

  15. Adoption Resource Directory: Region X.

    ERIC Educational Resources Information Center

    1983

    State, regional, and national adoption resources are described in this directory for residents of Region X states (Alaska, Idaho, Oregon, and Washington). Emphasizing the adoption of children with special needs, the directory gives organizational contacts for parents in various stages of the adoption process and mentions resources for social…

  16. Recruiting Mexican American Adoptive Parents.

    ERIC Educational Resources Information Center

    Bausch, Robert S.; Serpe, Richard T.

    1999-01-01

    Interviews were conducted with 591 Mexican Americans to determine adoption interest and create recruiting practices for prospective parents. Approximately one-third of sample reported an interest in adoption, but many perceived both structural and cultural obstacles to adoption. Based on findings, recommendations for increasing recruitment of…

  17. Male pregnancy and biparental immune priming.

    PubMed

    Roth, Olivia; Klein, Verena; Beemelmanns, Anne; Scharsack, Jörn P; Reusch, Thorsten B H

    2012-12-01

    In vertebrates, maternal transfer of immunity via the eggs or placenta provides offspring with crucial information on prevailing pathogens and parasites. Males contribute little to such transgenerational immune priming, either because they do not share the environment and parasite pressure of the offspring or because sperm are too small for transfer of immunity. In the teleost group of Syngnathids (pipefish, seahorses, and sea dragons), males brood female eggs in a placenta-like structure. Such sex-role-reversed species provide a unique opportunity to test for adaptive plasticity in immune transfer. Here, males and females should both influence offspring immunity. We experimentally tested paternal effects on offspring immunity by examining immune cell proliferation and immune gene expression. Maternal and paternal bacterial exposure induced offspring immune defense 5 weeks after hatching, and this effect persisted in 4-month-old offspring. For several offspring immune traits, double parental exposure (maternal and paternal) enhanced the response, whereas for another group of immune traits, the transgenerational induction already took place if only one parent was exposed. Our study shows that sex role reversal in connection with male pregnancy opens the door for biparental influences on offspring immunity and may represent an additional advantage for the evolution of male pregnancy. PMID:23149404

  18. Management of patients with non-Hodgkin’s lymphoma: focus on adoptive T-cell therapy

    PubMed Central

    Perna, Serena Kimi; Huye, Leslie E; Savoldo, Barbara

    2015-01-01

    Non-Hodgkin’s lymphoma (NHL) represents a heterogeneous group of malignancies with high diversity in terms of biology, clinical responses, and prognosis. Standard therapy regimens produce a 5-year relative survival rate of only 69%, with the critical need to increase the treatment-success rate of this patient population presenting at diagnosis with a median age of 66 years and many comorbidities. The evidence that an impaired immune system favors the development of NHL has opened the stage for new therapeutics, and specifically for the adoptive transfer of ex vivo-expanded antigen-specific T-cells. In this review, we discuss how T-cells specific for viral-associated antigens, nonviral-associated antigens expressed by the tumor, T-cells redirected through the expression of chimeric antigen receptors, and transgenic T-cell receptors against tumor cells have been developed and used in clinical trials for the treatment of patients with NHLs. PMID:27471712

  19. Intellectual resemblance among adoptive adoptive and biological relatives: the Texas adoption project.

    PubMed

    Horn, J M; Loehlin, J C; Willerman, L

    1979-05-01

    Intellectual and personality measures were available from unwed mothers who gave their children up for adoption at birth. The same or similar measures have been obtained from 300 sets of adoptive parents and all of their adopted and natural children in the Texas Adoption Project. The sample characteristics are discussed in detail, and the basic findings for IQ are presented. Initial analyses of the data on IQ suggest moderate heritabilities. Emphasis is placed on the preliminary nature of these findings.

  20. Technology Adoption: an Interaction Perspective

    NASA Astrophysics Data System (ADS)

    Sitorus, Hotna M.; Govindaraju, Rajesri; Wiratmadja, I. I.; Sudirman, Iman

    2016-02-01

    The success of a new technology depends on how well it is accepted by its intended users. Many technologies face the problem of low adoption rate, despite the benefits. An understanding of what makes people accept or reject a new technology can help speed up the adoption rate. This paper presents a framework for technology adoption based on an interactive perspective, resulting from a literature study on technology adoption. In studying technology adoption, it is necessary to consider the interactions among elements involved in the system, for these interactions may generate new characteristics or new relationships. The interactions among elements in a system adoption have not received sufficient consideration in previous studies of technology adoption. Based on the proposed interaction perspective, technology adoption is elaborated by examining interactions among the individual (i.e. the user or prospective user), the technology, the task and the environment. The framework is formulated by adopting several theories, including Perceived Characteristics of Innovating, Diffusion of Innovation Theory, Technology Acceptance Model, Task-Technology Fit and usability theory. The proposed framework is illustrated in the context of mobile banking adoption. It is aimed to offer a better understanding of determinants of technology adoption in various contexts, including technology in manufacturing systems.

  1. Adoption: medical and legal aspects.

    PubMed

    Bhalla, C K

    1978-06-01

    The problem of abandoned children is of great magnitude in India. Placement of these children in a family environment is essential for their physical, mental, and emotional development. Adoption must be approached from the child welfare perspective. The pediatrician can play an important role in the adoption process. The pediatrician should perform a thorough medical examination of infants to be adopted, both to ensure the child's welfare and to give adoptive parents an assessment of the child's health. Information should be collected on the medical history of the child's biologic parents to aid in the evaluation process. Adoptive parents should also undergo medical and pyschological examinations. Pediatricians can additionally work with social welfare departments in establishing criteria for matching children with adoptive parents. Adoptions in India are currently governed by provisions or the 1956 Hindu Adoptions and Maintenance Act. Since this legislation excludes groups such as Muslims, Christians, and Parsis from its purview, there has been a demand for national legislation providing a uniform adoption law for all the communities in India. The Union Government introduced such a comprehensive bill in 1972, the Adoption of Children Bill; however, no action was ever taken. It is urged that this legislation be reactivated, and that the restriction on the removal of children for adoption outside India be lifted. PMID:721273

  2. Intercountry versus Transracial Adoption: Analysis of Adoptive Parents' Motivations and Preferences in Adoption

    ERIC Educational Resources Information Center

    Zhang, Yuanting; Lee, Gary R.

    2011-01-01

    The United States is one of the major baby-receiving countries in the world. Relatively little research has focused on why there is such a high demand for intercountry adoption. Using in-depth qualitative interviews with adoptive parents, the authors explored the reasons why Americans prefer to adopt foreign-born children instead of adopting…

  3. A new immunization and treatment strategy for mouse mammary tumor virus (MMTV) associated cancers

    PubMed Central

    Braitbard, Ori; Roniger, Maayan; Bar-Sinai, Allan; Rajchman, Dana; Gross, Tamar; Abramovitch, Hillel; Ferla, Marco La; Franceschi, Sara; Lessi, Francesca; Naccarato, Antonio Giuseppe; Mazzanti, Chiara M.; Bevilacqua, Generoso; Hochman, Jacob

    2016-01-01

    Mouse Mammary Tumor Virus (MMTV) causes mammary carcinoma or lymphoma in mice. An increasing body of evidence in recent years supports its involvement also in human sporadic breast cancer. It is thus of importance to develop new strategies to impair the development, growth and metastasis of MMTV-associated cancers. The signal peptide of the envelope precursor protein of this virus: MMTV-p14 (p14) is an excellent target for such strategies, due to unique characteristics distinct from its regular endoplasmic reticulum targeting function. These include cell surface expression in: murine cancer cells that harbor the virus, human breast cancer (MCF-7) cells that ectopically express p14, as well as cultured human cells derived from an invasive ductal breast carcinoma positive for MMTV sequences. These findings support its use in signal peptide-based immune targeting. Indeed, priming and boosting mice with p14 elicits a specific anti-signal peptide immune response sufficient for protective vaccination against MMTV-associated tumors. Furthermore, passive immunization using a combination of anti-p14 monoclonal antibodies or the transfer of T-cells from immunized mice (Adoptive Cell Transfer) is also therapeutically effective. With reports demonstrating involvement of MMTV in human breast cancer, we propose the immune-mediated targeting of p14 as a strategy for prevention, treatment and diagnosis of MMTV-associated cancers. PMID:26934560

  4. Combining α-Radioimmunotherapy and Adoptive T Cell Therapy to Potentiate Tumor Destruction

    PubMed Central

    Ménager, Jérémie; Gorin, Jean-Baptiste; Maurel, Catherine; Drujont, Lucile; Gouard, Sébastien; Louvet, Cédric; Chérel, Michel; Faivre-Chauvet, Alain; Morgenstern, Alfred; Bruchertseifer, Frank; Davodeau, François

    2015-01-01

    Ionizing radiation induces direct and indirect killing of cancer cells and for long has been considered as immunosuppressive. However, this concept has evolved over the past few years with the demonstration that irradiation can increase tumor immunogenicity and can actually favor the implementation of an immune response against tumor cells. Adoptive T-cell transfer (ACT) is also used to treat cancer and several studies have shown that the efficacy of this immunotherapy was enhanced when combined with radiation therapy. α-Radioimmunotherapy (α-RIT) is a type of internal radiotherapy which is currently under development to treat disseminated tumors. α-particles are indeed highly efficient to destroy small cluster of cancer cells with minimal impact on surrounding healthy tissues. We thus hypothesized that, in the setting of α-RIT, an immunotherapy like ACT, could benefit from the immune context induced by irradiation. Hence, we decided to further investigate the possibilities to promote an efficient and long-lasting anti-tumor response by combining α-RIT and ACT. To perform such study we set up a multiple myeloma murine model which express the tumor antigen CD138 and ovalbumine (OVA). Then we evaluated the therapeutic efficacy in the mice treated with α-RIT, using an anti-CD138 antibody coupled to bismuth-213, followed by an adoptive transfer of OVA-specific CD8+ T cells (OT-I CD8+ T cells). We observed a significant tumor growth control and an improved survival in the animals treated with the combined treatment. These results demonstrate the efficacy of combining α-RIT and ACT in the MM model we established. PMID:26098691

  5. Harnessing the immune system to improve cancer therapy

    PubMed Central

    Papaioannou, Nikos E.; Beniata, Ourania V.; Vitsos, Panagiotis

    2016-01-01

    Cancer immunotherapy uses the immune system and its components to mount an anti-tumor response. During the last decade, it has evolved from a promising therapy option to a robust clinical reality. Many immunotherapeutic modalities are already approved by the Food and Drug Administration (FDA) for treating cancer patients and many others are in the pipeline for approval as standalone or combinatorial therapeutic interventions, several also combined with standard treatments in clinical studies. The two main axes of cancer immunotherapeutics refer to passive and active treatments. Prominent examples of passive immunotherapy include administration of monoclonal antibodies and cytokines and adoptive cell transfer of ex vivo “educated” immune cells. Active immunotherapy refers, among others, to anti-cancer vaccines [peptide, dendritic cell (DC)-based and allogeneic whole cell vaccines], immune checkpoint inhibitors and oncolytic viruses, whereas new approaches that can further enhance anti-cancer immune responses are also widely explored. Herein, we present the most popular cancer immunotherapy approaches and discuss their clinical relevance referring to data acquired from clinical trials. To date, clinical experience and efficacy suggest that combining more than one immunotherapy interventions, in conjunction with other treatment options like chemotherapy, radiotherapy and targeted or epigenetic therapy, should guide the way to cancer cure. PMID:27563648

  6. Th9 Cells Drive Host Immunity against Gastrointestinal Worm Infection.

    PubMed

    Licona-Limón, Paula; Henao-Mejia, Jorge; Temann, Angela U; Gagliani, Nicola; Licona-Limón, Ileana; Ishigame, Harumichi; Hao, Liming; Herbert, De'broski R; Flavell, Richard A

    2013-10-17

    Type 2 inflammatory cytokines, including interleukin-4 (IL-4), IL-5, IL-9, and IL-13, drive the characteristic features of immunity against parasitic worms and allergens. Whether IL-9 serves an essential role in the initiation of host-protective responses is controversial, and the importance of IL-9- versus IL-4-producing CD4⁺ effector T cells in type 2 immunity is incompletely defined. Herein, we generated IL-9-deficient and IL-9-fluorescent reporter mice that demonstrated an essential role for this cytokine in the early type 2 immunity against Nippostrongylus brasiliensis. Whereas T helper 9 (Th9) cells and type 2 innate lymphoid cells (ILC2s) were major sources of infection-induced IL-9 production, the adoptive transfer of Th9 cells, but not Th2 cells, caused rapid worm expulsion, marked basophilia, and increased mast cell numbers in Rag2-deficient hosts. Taken together, our data show a critical and nonredundant role for Th9 cells and IL-9 in host-protective type 2 immunity against parasitic worm infection.

  7. Harnessing the immune system to improve cancer therapy.

    PubMed

    Papaioannou, Nikos E; Beniata, Ourania V; Vitsos, Panagiotis; Tsitsilonis, Ourania; Samara, Pinelopi

    2016-07-01

    Cancer immunotherapy uses the immune system and its components to mount an anti-tumor response. During the last decade, it has evolved from a promising therapy option to a robust clinical reality. Many immunotherapeutic modalities are already approved by the Food and Drug Administration (FDA) for treating cancer patients and many others are in the pipeline for approval as standalone or combinatorial therapeutic interventions, several also combined with standard treatments in clinical studies. The two main axes of cancer immunotherapeutics refer to passive and active treatments. Prominent examples of passive immunotherapy include administration of monoclonal antibodies and cytokines and adoptive cell transfer of ex vivo "educated" immune cells. Active immunotherapy refers, among others, to anti-cancer vaccines [peptide, dendritic cell (DC)-based and allogeneic whole cell vaccines], immune checkpoint inhibitors and oncolytic viruses, whereas new approaches that can further enhance anti-cancer immune responses are also widely explored. Herein, we present the most popular cancer immunotherapy approaches and discuss their clinical relevance referring to data acquired from clinical trials. To date, clinical experience and efficacy suggest that combining more than one immunotherapy interventions, in conjunction with other treatment options like chemotherapy, radiotherapy and targeted or epigenetic therapy, should guide the way to cancer cure. PMID:27563648

  8. Successful attenuation of humoral immunity to viral capsid and transgenic protein following AAV mediated gene transfer with a non-depleting CD4 antibody and cyclosporine

    PubMed Central

    McIntosh, Jenny; Cochrane, Melanie; Cobbold, Stephen; Waldmann, Herman; Davidoff, Andrew M.; Nathwani, Amit C.

    2012-01-01

    The ability of transient immunosuppression with a combination of a nondepleting anti-CD4 (NDCD4) antibody and Cyclosporine (CyA) to abrogate immune reactivity to both adeno-associated virus vector (AAV) and its transgene product was evaluated. This combination of immunosuppressants resulted in a 20-fold reduction in the resulting anti-AAV8 antibody titres, to levels in naïve mice, following intravenous administration of 2×1012 AAV8 vector particles/kg to immunocompetent mice. This allowed efficient transduction upon secondary challenge with vector pseudotyped with the same capsid. Persistent tolerance did not result, however, as an anti-AAV8 antibody response was elicited upon rechallenge with AAV8 without immunosuppression. The route of vector administration, vector dose, AAV serotype or the concomitant administration of adenoviral vector appeared to have little impact on the ability of the NDCD4 antibody and CyA combination to moderate the primary humoral response to AAV capsid proteins. The combination of NDCD4 and CyA also abrogated the humoral response to the transgene product, that otherwise invariably would occur, following intramuscular injection of AAV5, leading to stable transgene expression. These observations could significantly improve the prospects of using rAAV vectors for chronic disorders by allowing for repeated vector administration and avoiding the development of antibodies to the transgene product. PMID:21716299

  9. Effect of Three Colostrum Diets on Passive Transfer of Immunity and Preweaning Health in Calves on a California Dairy following Colostrum Management Training

    PubMed Central

    Williams, Deniece R.; Pithua, Patrick; Garcia, Angel; Champagne, John; Haines, Deborah M.; Aly, Sharif S.

    2014-01-01

    Following colostrum management training, a randomized field trial was conducted on a California dairy to determine the effect of supplementing pooled colostrum with either colostrum-derived replacer (CDR) or second-milking colostrum (transition milk) on failure of passive transfer (FPT) and preweaning morbidity risks. A total of 166 calves were randomly assigned to 4L first-milking pooled colostrum (treatment 1), 2L first-milking pooled colostrum and 2L of CDR (treatment 2), or 2L first-milking pooled colostrum and 2L second-milking pooled colostrum (treatment 3). Mean 24-hour serum TP and IgG for treatments 2 (TP 5.2 g/dL, IgG 15.9 g/L) and 3 (TP 5.4 g/dL, IgG 18.3 g/L) did not statistically differ but were significantly lower than for treatment 1 (TP 5.9 g/dL, IgG 24.6 g/L). Risk of FPT did not differ for treatments 1, 2, and 3 (0.0%, 9.3%, and 1.9%, resp.). Similarly, the preweaning risk of diarrhea (81.0%, 92.5%, and 87.0%, resp.) or pneumonia (6.9%, 13.2%, and 18.5%, resp.) did not differ between treatments. Feeding 4L first-milking pooled colostrum resulted in adequate passive transfer. When first-milking pooled colostrum quantity is inadequate, CDR or second-milking pooled colostrum can be used to supplement the required colostrum volume and IgG mass without adversely affecting the risks of FPT or preweaning diarrhea and pneumonia. PMID:24864224

  10. Immune System

    EPA Science Inventory

    A properly functioning immune system is essential to good health. It defends the body against infectious agents and in some cases tumor cells. Individuals with immune deficiencies resulting from genetic defects, diseases (e.g., AIDS, leukemia), or drug therapies are more suscepti...

  11. Adoptive immunotherapy for acute leukemia: New insights in chimeric antigen receptors

    PubMed Central

    Heiblig, Maël; Elhamri, Mohamed; Michallet, Mauricette; Thomas, Xavier

    2015-01-01

    Relapses remain a major concern in acute leukemia. It is well known that leukemia stem cells (LSCs) hide in hematopoietic niches and escape to the immune system surveillance through the outgrowth of poorly immunogenic tumor-cell variants and the suppression of the active immune response. Despite the introduction of new reagents and new therapeutic approaches, no treatment strategies have been able to definitively eradicate LSCs. However, recent adoptive immunotherapy in cancer is expected to revolutionize our way to fight against this disease, by redirecting the immune system in order to eliminate relapse issues. Initially described at the onset of the 90’s, chimeric antigen receptors (CARs) are recombinant receptors transferred in various T cell subsets, providing specific antigens binding in a non-major histocompatibility complex restricted manner, and effective on a large variety of human leukocyte antigen-divers cell populations. Once transferred, engineered T cells act like an expanding “living drug” specifically targeting the tumor-associated antigen, and ensure long-term anti-tumor memory. Over the last decades, substantial improvements have been made in CARs design. CAR T cells have finally reached the clinical practice and first clinical trials have shown promising results. In acute lymphoblastic leukemia, high rate of complete and prolonged clinical responses have been observed after anti-CD19 CAR T cell therapy, with specific but manageable adverse events. In this review, our goal was to describe CAR structures and functions, and to summarize recent data regarding pre-clinical studies and clinical trials in acute leukemia. PMID:26328018

  12. Adoption and Assisted Reproduction. Adoption and Ethics, Volume 4.

    ERIC Educational Resources Information Center

    Freundlich, Madelyn

    The controversies in adoption have extended across a spectrum of policy and practice issues, and although the issues have become clear, resolution has not been achieved nor has consensus developed regarding a framework on which to improve the quality of adoption policy and practice. This book is the fourth in a series to use an ethics-based…

  13. The Market Forces in Adoption. Adoption and Ethics, Volume 2.

    ERIC Educational Resources Information Center

    Freundlich, Madelyn

    The controversies in adoption have extended across a spectrum of policy and practice issues, and although the issues have become clear, resolution has not been achieved nor has consensus developed regarding a framework on which to improve the quality of adoption policy and practice. This book is the second in a series to use an ethics-based…

  14. Homosexuality and adoption in Brazil.

    PubMed

    Uziel, A P

    2001-11-01

    Western societies are undergoing legal and policy changes in relation to laws governing the family, marital status, sexual orientation and the welfare of children, including in Brazil where, in the 1990s, the rights of homosexuals were incorporated into ongoing debates about what constitutes a family. This paper discusses the issue of adoption of children by homosexual men in Brazil, using information from court records from 1995-2000 in Rio de Janeiro, and from interviews with two judges, five psychologists and four social workers who evaluate those wishing to adopt. It uses the case records of one man's application to adopt, in which homosexuality became a central issue. Both the construction of masculinity in relation to parenting and concepts of the family were the parameters upon which the decision to allow him to adopt or not depended. Because the legislation does not specify what the sexual orientation of would-be adoptive parents should be, it is possible for single persons to adopt if they show they can be good parents. As more single people, alone or in couples, seek to adopt, it is important to clarify the criteria for judicial decisions on adoption applications. A dialogue is therefore needed on the meaning of family and whether and how it relates to sexual orientation. It is only on this basis that the courts can take a clear decision as to whether being homosexual is a relevant issue in regard to applications to adopt or not.

  15. Feasibility of Telomerase-Specific Adoptive T-cell Therapy for B-cell Chronic Lymphocytic Leukemia and Solid Malignancies.

    PubMed

    Sandri, Sara; Bobisse, Sara; Moxley, Kelly; Lamolinara, Alessia; De Sanctis, Francesco; Boschi, Federico; Sbarbati, Andrea; Fracasso, Giulio; Ferrarini, Giovanna; Hendriks, Rudi W; Cavallini, Chiara; Scupoli, Maria Teresa; Sartoris, Silvia; Iezzi, Manuela; Nishimura, Michael I; Bronte, Vincenzo; Ugel, Stefano

    2016-05-01

    Telomerase (TERT) is overexpressed in 80% to 90% of primary tumors and contributes to sustaining the transformed phenotype. The identification of several TERT epitopes in tumor cells has elevated the status of TERT as a potential universal target for selective and broad adoptive immunotherapy. TERT-specific cytotoxic T lymphocytes (CTL) have been detected in the peripheral blood of B-cell chronic lymphocytic leukemia (B-CLL) patients, but display low functional avidity, which limits their clinical utility in adoptive cell transfer approaches. To overcome this key obstacle hindering effective immunotherapy, we isolated an HLA-A2-restricted T-cell receptor (TCR) with high avidity for human TERT from vaccinated HLA-A*0201 transgenic mice. Using several relevant humanized mouse models, we demonstrate that TCR-transduced T cells were able to control human B-CLL progression in vivo and limited tumor growth in several human, solid transplantable cancers. TERT-based adoptive immunotherapy selectively eliminated tumor cells, failed to trigger a self-MHC-restricted fratricide of T cells, and was associated with toxicity against mature granulocytes, but not toward human hematopoietic progenitors in humanized immune reconstituted mice. These data support the feasibility of TERT-based adoptive immunotherapy in clinical oncology, highlighting, for the first time, the possibility of utilizing a high-avidity TCR specific for human TERT. Cancer Res; 76(9); 2540-51. ©2016 AACR.

  16. Adipose-Derived Mesenchymal Stem Cells Restore Impaired Mucosal Immune Responses in Aged Mice.

    PubMed

    Aso, Kazuyoshi; Tsuruhara, Akitoshi; Takagaki, Kentaro; Oki, Katsuyuki; Ota, Megumi; Nose, Yasuhiro; Tanemura, Hideki; Urushihata, Naoki; Sasanuma, Jinichi; Sano, Masayuki; Hirano, Atsuyuki; Aso, Rio; McGhee, Jerry R; Fujihashi, Kohtaro

    2016-01-01

    It has been shown that adipose-derived mesenchymal stem cells (AMSCs) can differentiate into adipocytes, chondrocytes and osteoblasts. Several clinical trials have shown the ability of AMSCs to regenerate these differentiated cell types. Age-associated dysregulation of the gastrointestinal (GI) immune system has been well documented. Our previous studies showed that impaired mucosal immunity in the GI tract occurs earlier during agingthan is seen in the systemic compartment. In this study, we examined the potential of AMSCs to restore the GI mucosal immune system in aged mice. Aged (>18 mo old) mice were adoptively transferred with AMSCs. Two weeks later, mice were orally immunized with ovalbumin (OVA) plus cholera toxin (CT) three times at weekly intervals. Seven days after the final immunization, when fecal extract samples and plasma were subjected to OVA- and CT-B-specific ELISA, elevated levels of mucosal secretory IgA (SIgA) and plasma IgG antibody (Ab) responses were noted in aged mouse recipients. Similar results were also seen aged mice which received AMSCs at one year of age. When cytokine production was examined, OVA-stimulated Peyer's patch CD4+ T cells produced increased levels of IL-4. Further, CD4+ T cells from the lamina propria revealed elevated levels of IL-4 and IFN-γ production. In contrast, aged mice without AMSC transfer showed essentially no OVA- or CT-B-specific mucosal SIgA or plasma IgG Ab or cytokine responses. Of importance, fecal extracts from AMSC transferred aged mice showed neutralization activity to CT intoxication. These results suggest that AMSCs can restore impaired mucosal immunity in the GI tract of aged mice. PMID:26840058

  17. Adipose-Derived Mesenchymal Stem Cells Restore Impaired Mucosal Immune Responses in Aged Mice

    PubMed Central

    Aso, Kazuyoshi; Tsuruhara, Akitoshi; Takagaki, Kentaro; Oki, Katsuyuki; Ota, Megumi; Nose, Yasuhiro; Tanemura, Hideki; Urushihata, Naoki; Sasanuma, Jinichi; Sano, Masayuki; Hirano, Atsuyuki; Aso, Rio; McGhee, Jerry R.; Fujihashi, Kohtaro

    2016-01-01

    It has been shown that adipose-derived mesenchymal stem cells (AMSCs) can differentiate into adipocytes, chondrocytes and osteoblasts. Several clinical trials have shown the ability of AMSCs to regenerate these differentiated cell types. Age-associated dysregulation of the gastrointestinal (GI) immune system has been well documented. Our previous studies showed that impaired mucosal immunity in the GI tract occurs earlier during agingthan is seen in the systemic compartment. In this study, we examined the potential of AMSCs to restore the GI mucosal immune system in aged mice. Aged (>18 mo old) mice were adoptively transferred with AMSCs. Two weeks later, mice were orally immunized with ovalbumin (OVA) plus cholera toxin (CT) three times at weekly intervals. Seven days after the final immunization, when fecal extract samples and plasma were subjected to OVA- and CT-B-specific ELISA, elevated levels of mucosal secretory IgA (SIgA) and plasma IgG antibody (Ab) responses were noted in aged mouse recipients. Similar results were also seen aged mice which received AMSCs at one year of age. When cytokine production was examined, OVA-stimulated Peyer’s patch CD4+ T cells produced increased levels of IL-4. Further, CD4+ T cells from the lamina propria revealed elevated levels of IL-4 and IFN-γ production. In contrast, aged mice without AMSC transfer showed essentially no OVA- or CT-B-specific mucosal SIgA or plasma IgG Ab or cytokine responses. Of importance, fecal extracts from AMSC transferred aged mice showed neutralization activity to CT intoxication. These results suggest that AMSCs can restore impaired mucosal immunity in the GI tract of aged mice. PMID:26840058

  18. Stories of Aboriginal Transracial Adoption

    ERIC Educational Resources Information Center

    Nuttgens, Simon

    2013-01-01

    Despite the significant number of transracial Aboriginal adoptions that have taken place in Canada, little research is available that addresses the psychological and psychosocial ramifications for the children involved. The scant literature that does exist raises concerns about the psychological impact of this type of adoption. The present…

  19. The Temporal Context of Adoption.

    ERIC Educational Resources Information Center

    Pontius, Steven K.

    This paper analyzes the amount of time required by farmers in four villages on the western edge of the central plain of Thailand to adopt four agricultural innovations--fertilizer, herbicide, insecticide, and fungicide. The general objective is to help researchers interested in the relationship of the adoption of new ideas to economic development…

  20. Adopting Children with Attachment Problems.

    ERIC Educational Resources Information Center

    Hughes, Daniel A.

    1999-01-01

    Notes that attachment behavior in infants is a facet of normal child development, and that children with attachment problems require special attention during and after the adoption process. Presents actions needed to increase the probability that such children can be successfully adopted, detailed attachment patterns, and parenting strategies and…

  1. Faculty Adoption of Educational Technology

    ERIC Educational Resources Information Center

    Moser, Franziska Zellweger

    2007-01-01

    Although faculty support has been identified as a critical factor in the success of educational-technology programs, many people involved in such efforts underestimate the complexities of integrating technology into teaching. In this article, the author proposes an adoption cycle to help tackle the complex issue of technology adoption for…

  2. Immunization Coverage

    MedlinePlus

    ... underused vaccines is increasing. Immunization currently averts an estimated 2 to 3 million deaths every year. An ... avoided, however, if global vaccination coverage improves. An estimated 19.4 million infants worldwide are still missing ...

  3. Adolescent immunization.

    PubMed

    Handal, G A

    2000-06-01

    The dramatic improvements achieved in the control of vaccine-preventable diseases in children have only been shared partially by adolescents and young adults, as today several million adolescents are not receiving the full complement of vaccines recommended by the Advisory Committee on Immunization Practices (ACIP). This article discusses the reasons for this problem and the tools to bridge this gap. In particular, medical societies and the Centers for Disease Control and Prevention (CDC) recommend a close assessment of the adolescentís immunization status between 11 and 12 years of age, inclusion of school immunization, and providing missing immunizations at any opportunity. The article also addresses other vaccines recommended for groups of adolescents with special needs, reporting information, and provides an update on the vaccines of the future.

  4. Characteristics of adopted juvenile delinquents.

    PubMed

    Kim, W J; Zrull, J P; Davenport, C W; Weaver, M

    1992-05-01

    There have been many reports describing the uniqueness of adopted children and adolescents' delinquent behaviors in terms of both their delinquent characteristics and courts' treatment of them. A total of 43 adopted juveniles, 32 extrafamilial (1.0%) and 11 intrafamilial (0.3%) adoptions were initially identified out of 3,280 juvenile delinquents. The adopted subjects were then compared with the demographically matched and offense matched nonadopted subjects. The family variables, such as marital and employment status of parents, were significantly different. However, there were only a few discernible trends, and in general there were no significant differences between the adopted and nonadopted juveniles in terms of their offense characteristics and dispositions. PMID:1592787

  5. 77 FR 48007 - Administrative Simplification: Adoption of Operating Rules for Health Care Electronic Funds...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-10

    ... the Health Care EFT Standards IFC (77 FR 1556). The standard for the ERA is the X12 835 TR3, adopted... Administrative Simplification: Adoption of Operating Rules for Health Care Electronic Funds Transfers (EFT) and... CFR Part 162 RIN 0938-AR01 Administrative Simplification: Adoption of Operating Rules for Health...

  6. Immunization with Escherichia coli outer membrane vesicles protects bacteria-induced lethality via Th1 and Th17 cell responses.

    PubMed

    Kim, Oh Youn; Hong, Bok Sil; Park, Kyong-Su; Yoon, Yae Jin; Choi, Seng Jin; Lee, Won Hee; Roh, Tae-Young; Lötvall, Jan; Kim, Yoon-Keun; Gho, Yong Song

    2013-04-15

    Outer membrane vesicles (OMVs), secreted from Gram-negative bacteria, are spherical nanometer-sized proteolipids enriched with outer membrane proteins. OMVs, also known as extracellular vesicles, have gained interests for use as nonliving complex vaccines and have been examined for immune-stimulating effects. However, the detailed mechanism on how OMVs elicit the vaccination effect has not been studied extensively. In this study, we investigated the immunological mechanism governing the protective immune response of OMV vaccines. Immunization with Escherichia coli-derived OMVs prevented bacteria-induced lethality and OMV-induced systemic inflammatory response syndrome. As verified by adoptive transfer and gene-knockout studies, the protective effect of OMV immunization was found to be primarily by the stimulation of T cell immunity rather than B cell immunity, especially by the OMV-Ag-specific production of IFN-γ and IL-17 from T cells. By testing the bacteria-killing ability of macrophages, we also demonstrated that IFN-γ and IL-17 production is the main factor promoting bacterial clearances. Our findings reveal that E. coli-derived OMV immunization effectively protects bacteria-induced lethality and OMV-induced systemic inflammatory response syndrome primarily via Th1 and Th17 cell responses. This study therefore provides a new perspective on the immunological detail regarding OMV vaccination. PMID:23514742

  7. Effects of maternal selenium supply and plane of nutrition during gestation on passive transfer of immunity and health in neonatal lambs.

    PubMed

    Hammer, C J; Thorson, J F; Meyer, A M; Redmer, D A; Luther, J S; Neville, T L; Reed, J J; Reynolds, L P; Caton, J S; Vonnahme, K A

    2011-11-01

    To investigate the influence of maternal Se supply and plane of nutrition on lamb morbidity, mortality, and passive transfer of IgG, pregnant ewe lambs were used in 2 experiments with 2 × 3 factorial treatment arrangements. Supplementation of Se began at breeding and was either adequate Se (ASe, 9.5 μg/kg of BW) or high Se (HSe, 81.8 μg/kg of BW) in Exp. 1 or ASe (11.5 µg/kg of BW) or HSe (77.0 µg/kg of BW) in Exp. 2. On d 50 or 40 of gestation for Exp. 1 or 2, respectively, ewes were assigned randomly to 1 of 3 nutritional planes: 60% (RES), 100% (control, CON), or 140% (HI) of NRC requirements. This resulted in the following treatments: ASe-RES, ASe-CON, ASe-HI, HSe-RES, HSe-CON, and HSe-HI. Upon parturition, lambs were separated from their dams and serum samples obtained. Lambs were fed artificial colostrum for the first 20 h and then placed on milk replacer and grain pellets until completion of the study (Exp. 1, 57 d; Exp. 2, 21 d). Twenty-four hours after parturition, lamb serum samples were collected for IgG analysis. All lambs were reared similarly and morbidity and mortality assessed. Main effects were considered significant when P ≤ 0.05. In Exp. 1, there was a Se × plane of nutrition interaction (P ≤ 0.01) for lamb morbidity from birth to weaning and for 24-h IgG concentration. Lambs from ASe-RES and HSe-HI ewes were treated more frequently (P < 0.01) for respiratory and gastrointestinal disease, and lambs from HSe-HI ewes had the smallest (P < 0.01) 24-h serum IgG concentration. In Exp. 1, lambs from HI ewes also had the greatest (P < 0.01) mortality rates from birth to weaning compared with lambs from CON and RES ewes. In Exp. 2, there was an effect (P < 0.01) of maternal plane of nutrition with lambs from RES ewes having increased 24-h IgG compared with lambs from CON and HI ewes. There was no effect of maternal Se supplementation on lamb 24-h IgG in Exp. 2; however, there was a Se × plane of nutrition interaction (P < 0.01) for morbidity

  8. The Place of Adoption in the NIDA Clinical Trials Network

    PubMed Central

    Jessup, Martha A.; Guydish, Joseph; Manser, Sarah Turcotte; Tajima, Barbara

    2009-01-01

    The National Institute on Drug Abuse (NIDA) Clinical Trials Network (CTN) was established in 1999 to determine effectiveness of drug abuse treatment interventions among diverse client populations and settings. To address dissemination of research findings, the CTN also has as its mission the transfer of research findings to treatment providers. In a qualitative study of adoption of evidence based practice in the context of two CTN clinical trials, we interviewed 29 participants from seven organizational levels of the multisite study organization about post-trial adoption, their role in the clinical trial, and interactions between the research initiative and clinic staff and setting. Analysis of interview data revealed a range of opinion among participants on the place of adoption within the CTN. Innovation within the CTN to support adoption and further observational research on dynamics of adoption within the CTN can increase dissemination of evidence-based drug abuse treatment interventions in the future. PMID:20126428

  9. In Vivo Expansion of Regulatory T cells With IL-2/IL-2 mAb Complexes Prevents Anti-factor VIII Immune Responses in Hemophilia A Mice Treated With Factor VIII Plasmid-mediated Gene Therapy

    PubMed Central

    Liu, Chao-Lien; Ye, Peiqing; Yen, Benjamin C; Miao, Carol H

    2011-01-01

    Generation of transgene-specific immune responses can constitute a major complication following gene therapy treatment. An in vivo approach to inducing selective expansion of Regulatory T (Treg) cells by injecting interleukin-2 (IL-2) mixed with a specific IL-2 monoclonal antibody (JES6-1) was adopted to modulate anti-factor VIII (anti-FVIII) immune responses. Three consecutive IL-2 complexes treatments combined with FVIII plasmid injection prevented anti-FVIII formation and achieved persistent, therapeutic-level of FVIII expression in hemophilia A (HemA) mice. The IL-2 complexes treatment expanded CD4+CD25+Foxp3+ Treg cells five- to sevenfold on peak day, and they gradually returned to normal levels within 7–14 days without changing other lymphocyte populations. The transiently expanded Treg cells are highly activated and display suppressive function in vitro. Adoptive transfer of the expanded Treg cells protected recipient mice from generation of high-titer antibodies following FVIII plasmid challenge. Repeated plasmid transfer is applicable in tolerized mice without eliciting immune responses. Mice treated with IL-2 complexes mounted immune responses against both T-dependent and T-independent neoantigens, indicating that IL-2 complexes did not hamper the immune system for long. These results demonstrate the important role of Treg cells in suppressing anti-FVIII immune responses and the potential of developing Treg cell expansion therapies that induce long-term tolerance to FVIII. PMID:21468007

  10. Determinants of Effective Information Transfer in International Regulatory Standards Adoption

    ERIC Educational Resources Information Center

    Popescu, Denisa

    2010-01-01

    The role of international regulatory standards within the current global environment has become of the most importance. The age of the global system and free market capitalism carried us into the unprecedented age of regulations, and standard setting. Regulations are now becoming the emerging mode of global governance. This study focuses on…

  11. Memory T cell–driven differentiation of naive cells impairs adoptive immunotherapy

    PubMed Central

    Klebanoff, Christopher A.; Scott, Christopher D.; Leonardi, Anthony J.; Yamamoto, Tori N.; Cruz, Anthony C.; Ouyang, Claudia; Ramaswamy, Madhu; Roychoudhuri, Rahul; Ji, Yun; Eil, Robert L.; Sukumar, Madhusudhanan; Crompton, Joseph G.; Palmer, Douglas C.; Borman, Zachary A.; Clever, David; Thomas, Stacy K.; Patel, Shashankkumar; Yu, Zhiya; Muranski, Pawel; Liu, Hui; Wang, Ena; Marincola, Francesco M.; Gros, Alena; Gattinoni, Luca; Rosenberg, Steven A.; Siegel, Richard M.; Restifo, Nicholas P.

    2015-01-01

    Adoptive cell transfer (ACT) of purified naive, stem cell memory, and central memory T cell subsets results in superior persistence and antitumor immunity compared with ACT of populations containing more-differentiated effector memory and effector T cells. Despite a clear advantage of the less-differentiated populations, the majority of ACT trials utilize unfractionated T cell subsets. Here, we have challenged the notion that the mere presence of less-differentiated T cells in starting populations used to generate therapeutic T cells is sufficient to convey their desirable attributes. Using both mouse and human cells, we identified a T cell–T cell interaction whereby antigen-experienced subsets directly promote the phenotypic, functional, and metabolic differentiation of naive T cells. This process led to the loss of less-differentiated T cell subsets and resulted in impaired cellular persistence and tumor regression in mouse models following ACT. The T memory–induced conversion of naive T cells was mediated by a nonapoptotic Fas signal, resulting in Akt-driven cellular differentiation. Thus, induction of Fas signaling enhanced T cell differentiation and impaired antitumor immunity, while Fas signaling blockade preserved the antitumor efficacy of naive cells within mixed populations. These findings reveal that T cell subsets can synchronize their differentiation state in a process similar to quorum sensing in unicellular organisms and suggest that disruption of this quorum-like behavior among T cells has potential to enhance T cell–based immunotherapies. PMID:26657860

  12. Serial Low Doses of Sorafenib Enhance Therapeutic Efficacy of Adoptive T Cell Therapy in a Murine Model by Improving Tumor Microenvironment

    PubMed Central

    Liu, Ren-Shyan; Hwang, Jeng-Jong

    2014-01-01

    Requirements of large numbers of transferred T cells and various immunosuppressive factors and cells in the tumor microenvironment limit the applications of adoptive T cells therapy (ACT) in clinic. Accumulating evidences show that chemotherapeutic drugs could act as immune supportive instead of immunosuppressive agents when proper dosage is used, and combined with immunotherapy often results in better treatment outcomes than monotherapy. Controversial immunomodulation effects of sorafenib, a multi-kinases inhibitor, at high and low doses have been reported in several types of cancer. However, what is the range of the low-dose sorafenib will influence the host immunity and responses of ACT is still ambiguous. Here we used a well-established E.G7/OT-1 murine model to understand the effects of serial low doses of sorafenib on both tumor microenvironment and transferred CD8+ T cells and the underlying mechanisms. Sorafenib lowered the expressions of immunosuppressive factors, and enhanced functions and migrations of transferred CD8+ T cells through inhibition of STAT3 and other immunosuppressive factors. CD8+ T cells were transduced with granzyme B promoter for driving imaging reporters to visualize the activation and distribution of transferred CD8+ T cells prior to adoptive transfer. Better activations of CD8+ T cells and tumor inhibitions were found in the combinational group compared with CD8+ T cells or sorafenib alone groups. Not only immunosuppressive factors but myeloid derived suppressive cells (MDSCs) and regulatory T cells (Tregs) were decreased in sorafenib-treated group, indicating that augmentation of tumor inhibition and function of CD8+ T cells by serial low doses of sorafenib were via reversing the immunosuppressive microenvironment. These results revealed that the tumor inhibitions of sorafenib not only through eradicating tumor cells but modifying tumor microenvironment, which helps outcomes of ACT significantly. PMID:25333973

  13. Ex vivo assessment of cellular immune function - applications in patient care and clinical studies.

    PubMed

    Lindemann, M

    2014-11-01

    Cellular ex vivo assays have a broad range of applications in patient care and clinical studies, especially when they are standardized and highly sensitive. As compared to analyses by molecular genetics such as the single nucleotide polymorphism (SNP) testing, they are usually more global. These assays partly mimic the in vivo situation, relying on a complex interaction of various immune cells. For example, they can be used to determine modulation of alloresponses by treatment or underlying disease, diagnose and quantify primary and secondary cellular immunodeficiency, follow-up vaccination responses, measure adoptive transfer of virus-specific immunity via hematopoietic stem cell or liver transplantation, assess allergy, antimicrobial immunity and also rare effector/memory cells directed against tumor antigens. This review will first shortly describe various cellular in vitro methods and then present applications, summarizing some own studies performed within the last 18 years. PMID:25329632

  14. The impact of regulatory T cells on T-cell immunity following hematopoietic cell transplantation

    PubMed Central

    Nguyen, Vu H.; Shashidhar, Sumana; Chang, Daisy S.; Ho, Lena; Kambham, Neeraja; Bachmann, Michael; Brown, Janice M.

    2008-01-01

    Regulatory T cells (Tregs) prevent graft-versus-host disease (GvHD) by inhibiting the proliferation and function of conventional T cells (Tcons). However, the impact of Tregs on T-cell development and immunity following hematopoietic cell transplantation (HCT) is unknown. Using a murine GvHD model induced by Tcons, we demonstrate that adoptive transfer of Tregs leads to (1) abrogration of GvHD, (2) preservation of thymic and peripheral lymph node architecture, and (3) an accelerated donor lymphoid reconstitution of a diverse TCR-Vβ repertoire. The resultant enhanced lymphoid reconstitution in Treg recipients protects them from lethal cytomegalovirus (MCMV) infection. By contrast, mice that receive Tcons alone have disrupted lymphoid organs from GvHD and remain lymphopenic with a restricted TCR-Vβ repertoire and rapid death on MCMV challenge. Lymphocytes from previously infected Treg recipients generate secondary response specific to MCMV, indicating long-term protective immunity with transferred Tregs. Thymectomy significantly reduces survival after MCMV challenge in Treg recipients compared with euthymic controls. Our results indicate that Tregs enhance immune reconstitution by preventing GvHD-induced damage of the thymic and secondary lymphoid microenvironment. These findings provide new insights into the role of Tregs in affording protection to lymphoid stromal elements important for T-cell immunity. PMID:17916743

  15. Internationally adopted children: a new challenge for pediatricians.

    PubMed

    Cataldo, F; Accomando, S; Porcari, V

    2006-02-01

    Children adopted from abroad by Italian families have increased during the last years. Since 2001 to 2004 they have been more than 10,000, mainly from Eastern Europe, and all indications suggest that they will continue to increase. Most of the internationally adopted children reside in orphanage before adoption where they may experience malnutrition, exposure to infectious diseases, environmental deprivation, neglect. Moreover, their pre-adoptive records are scarcely reliable and their immunization status is not always adequate. The most common long-term problems of internationally adopted children concern developmental and scholastic delay especially if they come from a long and severely deprived institutional setting, precocious puberty and, during adolescence, depressive disorders as well as antisocial behaviours. Inter-country adopted children are at increased risk for health and social problems and have to be recognized as a group of subjects requiring special medical attentions. Specialized centres for internationally adopted children where they could receive medical evaluations upon arrival and a prolonged health follow-up should be set up. PMID:16541007

  16. Counseling Issues in Adoptions by Stepparents.

    ERIC Educational Resources Information Center

    Wolf, Patricia A.; Mast, Emily

    1987-01-01

    Although the number of nonrelative adoptions is decreasing, stepparent adoptions are not. These adoptions are viewed as nonproblematic family business separate from the general adoption picture. This article examines demographic data in Lancaster County, Pennsylvania, from 55 stepparent adoptions concerning stepparent adopters, birth parents, and…

  17. HLA-peptide multimer selection of adenovirus-specific T cells for adoptive T-cell therapy.

    PubMed

    Chakupurakal, Geothy; Onion, David; Bonney, Sarah; Cobbold, Mark; Mautner, Vivien; Moss, Paul

    2013-10-01

    Adenovirus (Ad) infection is a cause of significant morbidity and mortality in hematopoietic stem cell transplant recipients and virus-specific immunotherapy is one option for improved control. Cellular immunity is an important component in suppression of Ad replication but the frequency and population distribution of Ad-specific CD8 T cells has not been systematically investigated. This is an important question in relation to the potential use of these cells for adoptive transfer. To address this question, HLA-peptide multimers were generated for 8 HLA class I-restricted Ad epitopes, which are highly conserved across Ad species. Epitope-specific CD8 T cells from healthy donors were identified by tetramer staining and HLA class I A*01-restricted TDL peptide staining T cells were characterized in relation to frequency, phenotype, and function. The cells demonstrated a minimally differentiated central memory phenotype (CD45RA, CD45RO, CCR7, CD62L, CD27, CD28, and CD57) and were able to produce IFN-γ and proliferate extensively upon antigen stimulation in vitro. After proliferation, the phenotype switched to CD45RO, although it is interesting to note that CCR7 expression was retained. Despite their low frequency, tetramer-staining cells could be enriched with magnetic bead technology. Their characteristics should permit rapid establishment in vivo post adoptive transfer, increasing therapeutic options for patients with Ad infection. This is the first reported characterization of Ad-specific tetramer-staining T cells with a view to adoptive transfer to hematopoietic stem cell transplant patients with Ad infection. The efficacy of these cells needs to be further evaluated in the setting of a clinical trial. PMID:23994889

  18. Adult immunization

    PubMed Central

    Mehta, Bharti; Chawla, Sumit; Kumar Dharma, Vijay; Jindal, Harashish; Bhatt, Bhumika

    2014-01-01

    Vaccination is recommended throughout life to prevent vaccine-preventable diseases and their sequel. The primary focus of vaccination programs has historically been directed to childhood immunizations. For adults, chronic diseases have been the primary focus of preventive and medical health care, though there has been increased emphasis on preventing infectious diseases. Adult vaccination coverage, however, remains low for most of the routinely recommended vaccines. Though adults are less susceptible to fall prey to traditional infectious agents, the probability of exposure to infectious agents has increased manifold owing to globalization and increasing travel opportunities both within and across the countries. Thus, there is an urgent need to address the problem of adult immunization. The adult immunization enterprise is more complex, encompassing a wide variety of vaccines and a very diverse target population. There is no coordinated public health infrastructure to support an adult immunization program as there is for children. Moreover, there is little coordination among adult healthcare providers in terms of vaccine provision. Substantial improvement in adult vaccination is needed to reduce the health consequences of vaccine-preventable diseases among adults. Routine assessment of adult patient vaccination needs, recommendation, and offer of needed vaccines for adults should be incorporated into routine clinical care of adults. PMID:24128707

  19. Plant Immunity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Plants are faced with defending themselves against a multitude of pathogens, including bacteria, fungi, viruses, nematodes, etc. Immunity is multi-layered and complex. Plants can induce defenses when they recognize small peptides, proteins or double-stranded RNA associated with pathogens. Recognitio...

  20. MicroRNA-155 Drives TH17 Immune Response and Tissue Injury in Experimental Crescentic GN

    PubMed Central

    Krebs, Christian F.; Kapffer, Sonja; Paust, Hans-Joachim; Schmidt, Tilman; Bennstein, Sabrina B.; Peters, Anett; Stege, Gesa; Brix, Silke R.; Meyer-Schwesinger, Catherine; Müller, Roman-Ulrich; Turner, Jan-Eric; Steinmetz, Oliver M.; Wolf, Gunter; Stahl, Rolf A. K.

    2013-01-01

    CD4+ T cells play a pivotal role in the pathogenesis of autoimmune disease, including human and experimental crescentic GN. Micro-RNAs (miRs) have emerged as important regulators of immune cell development, but the impact of miRs on the regulation of the CD4+ T cell immune response remains to be fully clarified. Here, we report that miR-155 expression is upregulated in the kidneys of patients with ANCA-associated crescentic GN and a murine model of crescentic GN (nephrotoxic nephritis). To elucidate the potential role of miR-155 in T cell-mediated inflammation, nephritis was induced in miR-155−/− and wild-type mice. The systemic and renal nephritogenic TH17 immune response decreased markedly in nephritic miR-155−/− mice. Consistent with this finding, miR-155–deficient mice developed less severe nephritis, with reduced histologic and functional injury. Adoptive transfer of miR-155−/− and wild-type CD4+ T cells into nephritic recombination activating gene 1-deficient (Rag-1−/−) mice showed the T cell-intrinsic importance of miR-155 for the stability of pathogenic TH17 immunity. These findings indicate that miR-155 drives the TH17 immune response and tissue injury in experimental crescentic GN and show that miR-155 is a potential therapeutic target in TH17-mediated diseases. PMID:23949802

  1. Activation of antitumor immune responses by Ganoderma formosanum polysaccharides in tumor-bearing mice.

    PubMed

    Wang, Cheng-Li; Lu, Chiu-Ying; Hsueh, Ying-Chao; Liu, Wen-Hsiung; Chen, Chun-Jen

    2014-11-01

    Fungi of the genus Ganoderma are basidiomycetes that have been used as traditional medicine in Asia and have been shown to exhibit various pharmacological activities. We recently found that PS-F2, a polysaccharide fraction purified from the submerged culture broth of Ganoderma formosanum, stimulates the maturation of dendritic cells and primes a T helper 1 (Th1)-polarized adaptive immune response in vivo. In this study, we investigated whether the immune adjuvant function of PS-F2 can stimulate antitumor immune responses in tumor-bearing mice. Continuous intraperitoneal or oral administration of PS-F2 effectively suppressed the growth of colon 26 (C26) adenocarcinoma, B16 melanoma, and sarcoma 180 (S180) tumor cells in mice without adverse effects on the animals' health. PS-F2 did not cause direct cytotoxicity on tumor cells, and it lost the antitumor effect in mice with severe combined immunodeficiency (SCID). CD4(+) T cells, CD8(+) T cells, and serum from PS-F2-treated tumor-bearing mice all exhibited antitumor activities when adoptively transferred to naïve animals, indicating that PS-F2 treatment stimulates tumor-specific cellular and humoral immune responses. These data demonstrate that continuous administration of G. formosanum polysaccharide PS-F2 can activate host immune responses against ongoing tumor growth, suggesting that PS-F2 can potentially be developed into a preventive/therapeutic agent for cancer immunotherapy.

  2. Role of maternally derived immunity in fish.

    PubMed

    Swain, P; Nayak, S K

    2009-08-01

    Maternal immunity is of paramount importance for protection of young ones at early stage of life since the immune factors of an immunocompetent female are transferred transplacentally or through colostrum, milk or yolk to an immunologically naive neonate. Both innate and adaptive type of immunity are transferred of from mother to offspring in fishes. These factors include immunoglobulin (Ig)/antibody, complement factors, lysozymes, protease inhibitors like alpha macroglobulin, different types of lectins and serine proteases like molecules. Among different types of Ig viz. IgM, IgD, IgT/IgZ and IgM-IgZ chimera types, IgM is present in most of the teleostean fishes. In teleosts, IgM either as a reduced/breakdown product or monomeric form is usually transferred to the offsprings. The maternally derived IgM usually persists for a limited duration, exhausts within the completion of yolk absorption process, and completely disappears thereafter during larval stages. Maternal transfer of immunity which provides defense to embryo and larvae depends upon the health as well as the immune status of brood fish. The overall health status of brood fish can affect breeding performances, quality seed production and protection of offsprings. However, factors such as age, maturation, reproductive behaviour and nutrition (micro and macro-nutrients) may affect the immunity in brood fishes. Besides these, seasonal changes such as photoperiods, temperature, adverse environmental conditions, and stress conditions like handling, crowding, and water pollution/contamination can also affect the immunity of brood fishes. The maintenance of the brood stock immunity at high level during vitellogenesis and oogenesis, is utmost important for reducing mortalities at larval/post larval stages through maximum/optimum transfer of maternal immunity. Brood stock immunization prior to breeding as well as selective breeding among the disease resistant families might be the ideal criteria for producing

  3. Immune System

    MedlinePlus

    ... addressing this critical issue? The combination of new technology and expanded genetic information promises to reveal more ... Substitution Scanning Electron Microscopy (SEM) Transmission Electron Microscopy Technology Transfer & Intellectual Property Model Agreements & Definitions Model Licenses ...

  4. Adoptive Immunotherapy for Hematological Malignancies Using T Cells Gene-Modified to Express Tumor Antigen-Specific Receptors

    PubMed Central

    Fujiwara, Hiroshi

    2014-01-01

    Accumulating clinical evidence suggests that adoptive T-cell immunotherapy could be a promising option for control of cancer; evident examples include the graft-vs-leukemia effect mediated by donor lymphocyte infusion (DLI) and therapeutic infusion of ex vivo-expanded tumor-infiltrating lymphocytes (TIL) for melanoma. Currently, along with advances in synthetic immunology, gene-modified T cells retargeted to defined tumor antigens have been introduced as “cellular drugs”. As the functional properties of the adoptive immune response mediated by T lymphocytes are decisively regulated by their T-cell receptors (TCRs), transfer of genes encoding target antigen-specific receptors should enable polyclonal T cells to be uniformly redirected toward cancer cells. Clinically, anticancer adoptive immunotherapy using genetically engineered T cells has an impressive track record. Notable examples include the dramatic benefit of chimeric antigen receptor (CAR) gene-modified T cells redirected towards CD19 in patients with B-cell malignancy, and the encouraging results obtained with TCR gene-modified T cells redirected towards NY-ESO-1, a cancer-testis antigen, in patients with advanced melanoma and synovial cell sarcoma. This article overviews the current status of this treatment option, and discusses challenging issues that still restrain the full effectiveness of this strategy, especially in the context of hematological malignancy. PMID:25517545

  5. Personality disorders in adopted versus non-adopted adults.

    PubMed

    Westermeyer, Joseph; Yoon, Gihyun; Amundson, Carla; Warwick, Marion; Kuskowski, Michael A

    2015-04-30

    The goal of this epidemiological study was to investigate lifetime history and odds ratios of personality disorders in adopted and non-adopted adults using a nationally representative sample. Data, drawn from the National Epidemiological Survey on Alcohol and Related Conditions (NESARC), were compared in adopted (n=378) versus non-adopted (n=42,503) adults to estimate the odds of seven personality disorders using logistic regression analyses. The seven personality disorders were histrionic, antisocial, avoidant, paranoid, schizoid, obsessive-compulsive, and dependent personality disorder. Adoptees had a 1.81-fold increase in the odds of any personality disorder compared with non-adoptees. Adoptees had increased odds of histrionic, antisocial, avoidant, paranoid, schizoid, and obsessive-compulsive personality disorder compared with non-adoptees. Two risk factors associated with lifetime history of a personality disorder in adoptees compared to non-adoptees were (1) being in the age cohort 18-29 years (but no difference in the age 30-44 cohort), using the age 45 or older cohort as the reference and (2) having 12 years of education (but no difference in higher education groups), using the 0-11 years of education as the reference. These findings support the higher rates of personality disorders among adoptees compared to non-adoptees.

  6. Re an Adoption Application (Surrogacy)

    PubMed

    1987-03-01

    In England, it is illegal under the Adoption Act 1958 to pay or reward anyone in an effort to adopt a child. A family court was asked in this case whether a surrogacy arrangement involving the payment of 5,000 pounds violated the Act. The applicants, a husband and wife, were unable to have children and had entered into an informal arrangement with a woman who agreed to engage in sexual intercourse with the husband and bear a child for the couple in exchange for 10,000 pounds. Because the surrogate wrote a book about her experience from which she made money, and sincerely wanted to help out the childless couple, she accepted only half of her fee. Convinced that the surrogate arrangement was not commercial in nature, the court found no violation of English law, authorized the payment to the mother, and authorized adoption of the child by the father and his wife.

  7. Vaccines for established cancer: overcoming the challenges posed by immune evasion.

    PubMed

    van der Burg, Sjoerd H; Arens, Ramon; Ossendorp, Ferry; van Hall, Thorbald; Melief, Cornelis J M

    2016-04-01

    Therapeutic vaccines preferentially stimulate T cells against tumour-specific epitopes that are created by DNA mutations or oncogenic viruses. In the setting of premalignant disease, carcinoma in situ or minimal residual disease, therapeutic vaccination can be clinically successful as monotherapy; however, in established cancers, therapeutic vaccines will require co-treatments to overcome immune evasion and to become fully effective. In this Review, we discuss the progress that has been made in overcoming immune evasion controlled by tumour cell-intrinsic factors and the tumour microenvironment. We summarize how therapeutic benefit can be maximized in patients with established cancers by improving vaccine design and by using vaccines to increase the effects of standard chemotherapies, to establish and/or maintain tumour-specific T cells that are re-energized by checkpoint blockade and other therapies, and to sustain the antitumour response of adoptively transferred T cells.

  8. Evaluation of innate and adaptive immunity contributing to the antitumor effects of PD1 blockade in an orthotopic murine model of pancreatic cancer.

    PubMed

    D'Alincourt Salazar, Marcela; Manuel, Edwin R; Tsai, Weimin; D'Apuzzo, Massimo; Goldstein, Leanne; Blazar, Bruce R; Diamond, Don J

    2016-06-01

    Despite the clinical success of anti-PD1 antibody (α-PD1) therapy, the immune mechanisms contributing to the antineoplastic response remain unclear. Here, we describe novel aspects of the immune response involved in α-PD1-induced antitumor effects using an orthotopic Kras (G12D)/p53(R172H)/Pdx1-Cre (KPC) model of pancreatic ductal adenocarcinoma (PDA). We found that positive therapeutic outcome involved both the innate and adaptive arms of the immune system. Adoptive transfer of total splenocytes after short-term (3 d) but not long-term (28 d) PD1 blockade significantly extended survival of non-treated tumor-bearing recipient mice. This protective effect appeared to be mostly mediated by T cells, as adoptive transfer of purified natural killer (NK) cells and/or granulocyte receptor 1 (Gr1)(+) cells or splenocytes depleted of Gr1(+) cells and NK cells did not exhibit transferrable antitumor activity following short-term PD1 blockade. Nevertheless, splenic and tumor-derived CD11b(+)Gr1(+) cells and NK cells showed significant persistence of α-PD1 bound to these cells in the treated primary recipient mice. We observed that short-term inhibition of PD1 signaling modulated the profiles of multifunctional cytokines in the tumor immune-infiltrate, including downregulation of vascular endothelial growth factor A (VEGF-A). Altogether, the data suggest that systemic blockade of PD1 results in rapid modulation of antitumor immunity that differs in the tumor microenvironment (TME) when compared to the spleen. These results demonstrate a key role for early immune-mediated events in controlling tumor progression in response to α-PD1 treatment and warrant further investigation into the mechanisms governing responses to the therapy at the innate-adaptive immune interface. PMID:27471630

  9. Adopting Internet Standards for Orbital Use

    NASA Technical Reports Server (NTRS)

    Wood, Lloyd; Ivancic, William; da Silva Curiel, Alex; Jackson, Chris; Stewart, Dave; Shell, Dave; Hodgson, Dave

    2005-01-01

    After a year of testing and demonstrating a Cisco mobile access router intended for terrestrial use onboard the low-Earth-orbiting UK-DMC satellite as part of a larger merged ground/space IP-based internetwork, we reflect on and discuss the benefits and drawbacks of integration and standards reuse for small satellite missions. Benefits include ease of operation and the ability to leverage existing systems and infrastructure designed for general use, as well as reuse of existing, known, and well-understood security and operational models. Drawbacks include cases where integration work was needed to bridge the gaps in assumptions between different systems, and where performance considerations outweighed the benefits of reuse of pre-existing file transfer protocols. We find similarities with the terrestrial IP networks whose technologies we have adopted and also some significant differences in operational models and assumptions that must be considered.

  10. Immunization Schedules for Adults

    MedlinePlus

    ... ACIP Vaccination Recommendations Why Immunize? Vaccines: The Basics Immunization Schedules for Adults in Easy-to-read Formats ... previous immunizations. View or Print a Schedule Recommended Immunizations for Adults (19 Years and Older) by Age ...

  11. Mutual Interference between Cytomegalovirus and Reconstitution of Protective Immunity after Hematopoietic Cell Transplantation.

    PubMed

    Reddehase, Matthias J

    2016-01-01

    Hematopoietic cell transplantation (HCT) is a therapy option for aggressive forms of hematopoietic malignancies that are resistant to standard antitumoral therapies. Hematoablative treatment preceding HCT, however, opens a "window of opportunity" for latent Cytomegalovirus (CMV) by releasing it from immune control with the consequence of reactivation of productive viral gene expression and recurrence of infectious virus. A "window of opportunity" for the virus represents a "window of risk" for the patient. In the interim between HCT and reconstitution of antiviral immunity, primarily mediated by CD8(+) T cells, initially low amounts of reactivated virus can expand exponentially, disseminate to essentially all organs, and cause multiple organ CMV disease, with interstitial pneumonia (CMV-IP) representing the most severe clinical manifestation. Here, I will review predictions originally made in the mouse model of experimental HCT and murine CMV infection, some of which have already paved the way to translational preclinical research and promising clinical trials of a preemptive cytoimmunotherapy of human CMV disease. Specifically, the mouse model has been pivotal in providing "proof of concept" for preventing CMV disease after HCT by adoptive transfer of preselected, virus epitope-specific effector and memory CD8(+) T cells bridging the critical interim. However, CMV is not a "passive antigen" but is a pathogen that actively interferes with the reconstitution of protective immunity by infecting bone marrow (BM) stromal cells that otherwise form niches for hematopoiesis by providing the structural microenvironment and by producing hematopoietically active cytokines, the hemopoietins. Depending on the precise conditions of HCT, reduced homing of transplanted hematopoietic stem- and progenitor cells to infected BM stroma and impaired colony growth and lineage differentiation can lead to "graft failure." In consequence, uncontrolled virus spread causes morbidity and

  12. Why Adoption of Standards Matters

    ERIC Educational Resources Information Center

    Journal of Staff Development, 2016

    2016-01-01

    A total of 39 states have adopted, adapted, or endorsed the Standards for Professional Learning, including the standards issued in 2011 (labeled in red) and those published earlier (labeled in blue). Making a commitment to the standards is a commitment to continuous learning for all educators in a school.

  13. Internet Adoption: An Empirical Investigation

    ERIC Educational Resources Information Center

    Ma, Junzhao

    2011-01-01

    The Internet has brought significant changes to the retail industry because it revolutionizes how information is transmitted and accessed. The main objective of this research is to enhance our understanding of people's adoption of the Internet and its implications for retail competition. This dissertation consists of two essays. The first essay…

  14. Has the Academy Adopted TQM?

    ERIC Educational Resources Information Center

    Birnbaum, Robert; Deshotels, Judy

    1999-01-01

    A survey of 469 colleges and universities assessed the degree to which colleges and universities have adopted total quality management (TQM) or continuous quality improvement (CQI) techniques. Results suggest use of TQM/CQI is lower than predicted, at about 13% of institutions. Variations in extent of use of the approach are discussed. (MSE)

  15. YB-1 immunization combined with regulatory T-cell depletion induces specific T-cell responses that protect against neuroblastoma in the early stage.

    PubMed

    Zheng, Jin; Liu, Ping; Yang, Xiaofeng

    2012-12-01

    Neuroblastoma is the most common extracranial solid cancer in childhood and the most common cancer in infancy. Currently, no effective clinical treatments are available for advanced neuroblastoma. In a previous study, we screened Y Box protein 1 (YB-1) as a potential neuroblastoma-associated antigen from sera of AGN2a-immunized mice by serological analysis of recombinant cDNA expression libraries technique. The aim of this study is to explore if YB-1 immunization in the context of Treg depletion could induce protective immune response against the neuroblastoma in mice. YB-1 was expressed and purified by pET-15b prokaryotic expression system. It was demonstrated that anti-YB-1 CD8(+) T-cell responses could be induced by AGN2a immunization, and the strongest CD8(+) T-cell responses against AGN2a were induced by YB-1-immunized mice in the context of Treg depletion compared with YB-1 only immunization group and control group. Importantly, the survival rate of mice treated with YB-1 immunization combined with Treg depletion was 80% when challenged by 1 × 10(4) AGN2a cells, significantly higher than that of mice immunized with YB-1 alone (P < 0.01). Furthermore, T-cell adoptive therapy showed that the neuroblastoma growth was inhibited when T cells or splenic cells from YB-1-immunized mice with Treg depletion were transferred to AGN2a bearing mice. Both CD4(+) and CD8(+) T cells were involved in the anti-neuroblastoma responses induced by YB-1 immunization combined with Treg depletion. These results indicated that YB-1 immunization combined with Treg depletion could induce specific T-cell responses against neuroblastoma and could be a potential strategy for the prevention and treatment of neuroblastoma in the early stage.

  16. Beyond "Technology Transfer"?

    ERIC Educational Resources Information Center

    van Beek, P. G. H.

    1997-01-01

    When agricultural innovations are not adopted, there is often a gap between what people know they ought to do and what they do. Extension practice needs to expand from technology transfer. The knowledge systems approach is useful in dealing with the introduction of innovation in increasingly complex and uncertain situations. (SK)

  17. Enhancement of antitumor immunity in lung cancer by targeting myeloid-derived suppressor cell pathways

    PubMed Central

    Sawant, Anandi; Schafer, Cara C.; Jin, Tong Huan; Zmijewski, Jaroslaw; Tse, Hubert M.; Roth, Justin; Sun, Zhihuan; Siegal, Gene P.; Thannickal, Victor J.; Grant, Stefan C.; Ponnazhagan, Selvarangan; Deshane, Jessy S.

    2013-01-01

    Chemoresistance due to heterogeneity of the tumor microenvironment (TME) hampers the long-term efficacy of frontline therapies for lung cancer. Current combination therapies for lung cancer provide only modest improvement in survival, implicating necessity for novel approaches that suppress malignant growth and stimulate long-term anti-tumor immunity. Oxidative stress in the TME promotes immunosuppression by tumor infiltrating myeloid-derived suppressor cells (MDSC), which inhibit host protective anti-tumor immunity. Using a murine model of lung cancer, we demonstrate that a combination treatment with gemcitabine and a superoxide dismutase mimetic targets immunosuppressive MDSC in the TME and enhances the quantity and quality of both effector and memory CD8+ T cell responses. At the effector cell function level, the unique combination therapy targeting MDSC and redox signaling greatly enhanced cytolytic CD8+ T cell response and further decreased T regulatory cell infiltration. For long-term anti-tumor effects, this therapy altered the metabolism of memory cells with self-renewing phenotype and provided a preferential advantage for survival of memory subsets with long-term efficacy and persistence. Adoptive transfer of memory cells from this combination therapy prolonged survival of tumor-bearing recipients. Furthermore, the adoptively-transferred memory cells responded to tumor re-challenge exerting long-term persistence. This approach offers a new paradigm to inhibit immunosuppression by direct targeting of MDSC function, generate effector and persistent memory cells for tumor eradication, and prevent lung cancer relapse. PMID:24085788

  18. Depletion of CD25⁺ T cells from hematopoietic stem cell grafts increases posttransplantation vaccine-induced immunity to neuroblastoma.

    PubMed

    Jing, Weiqing; Yan, Xiaocai; Hallett, William H D; Gershan, Jill A; Johnson, Bryon D

    2011-06-23

    A multifaceted immunotherapeutic strategy that includes hematopoietic stem cell (HSC) transplantation, T-cell adoptive transfer, and tumor vaccination can effectively eliminate established neuroblastoma tumors in mice. In vivo depletion of CD4⁺ T cells in HSC transplantation recipients results in increased antitumor immunity when adoptively transferred T cells are presensitized, but development of T-cell memory is severely compromised. Because increased percentages of regulatory T (Treg) cells are seen in HSC transplantation recipients, here we hypothesized that the inhibitory effect of CD4⁺ T cells is primarily because of the presence of expanded Treg cells. Remarkably, adoptive transfer of presensitized CD25-depleted T cells increased tumor vaccine efficacy. The enhanced antitumor effect achieved by ex vivo depletion of CD25⁺ Treg cells was similar to that achieved by in vivo depletion of all CD4⁺ T cells. Depletion of CD25⁺ Treg cells resulted in elevated frequencies of tumor-reactive CD8 and CD4⁺ T cells and increased CD8-to-Treg cell ratios inside tumor masses. All mice given presensitized CD25-depleted T cells survived a tumor rechallenge, indicating the development of long-term CD8⁺ T-cell memory to tumor antigens. These observations should aid in the future design of immunotherapeutic approaches that promote the generation of both acute and long-term antitumor immunity.

  19. Curcumin and tumor immune-editing: resurrecting the immune system.

    PubMed

    Bose, Sayantan; Panda, Abir Kumar; Mukherjee, Shravanti; Sa, Gaurisankar

    2015-01-01

    Curcumin has long been known to posses medicinal properties and recent scientific studies have shown its efficacy in treating cancer. Curcumin is now considered to be a promising anti-cancer agent and studies continue on its molecular mechanism of action. Curcumin has been shown to act in a multi-faceted manner by targeting the classical hallmarks of cancer like sustained proliferation, evasion of apoptosis, sustained angiogenesis, insensitivity to growth inhibitors, tissue invasion and metastasis etc. However, one of the emerging hallmarks of cancer is the avoidance of immune system by tumors. Growing tumors adopt several strategies to escape immune surveillance and successfully develop in the body. In this review we highlight the recent studies that show that curcumin also targets this process and helps restore the immune activity against cancer. Curcumin mediates several processes like restoration of CD4(+)/CD8(+) T cell populations, reversal of type-2 cytokine bias, reduction of Treg cell population and suppression of T cell apoptosis; all these help to resurrect tumor immune surveillance that leads to tumor regression. Thus interaction of curcumin with the immune system is also an important feature of its multi-faceted modes of action against cancer. Finally, we also point out the drawbacks of and difficulties in curcumin administration and indicate the use of nano-formulations of curcumin for better therapeutic efficacy. PMID:26464579

  20. Immune cells tracing using quantum dots

    NASA Astrophysics Data System (ADS)

    Hoshino, Akiyoshi; Fujioka, Kouki; Kawamura, Yuki I.; Toyama-Sorimachi, Noriko; Yasuhara, Masato; Dohi, Taeko; Yamamoto, Kenji

    2006-02-01

    Fluorescent nanoparticles, such as nanocrystal quantum dots (QDs), have potential to be applied to molecular biology and bioimaging, since some nanocrystals emit higher and longer lasting fluorescence than conventional organic probes do. Here we report an example of labeling immune cells by QDs. We collected splenic CD4 + T-lymphocyte and peritoneal macrophages from mice. Then cells were labeled with QDs. QDs are incorporated into the T-lymphocyte and macrophages immediately after addition and located in the cytoplasm via endocytosis pathway. The fluorescence of QDs held in the endosomes was easily detected for more than a week. In addition, T-lymphocytes labeled with QDs were stable and cell proliferation or cytokine production including IL-2 and IFN-γ was not affected. When QD-labeled T-lymphocytes were adoptively transferred intravenously to mice, they remained in the peripheral blood and spleen up to a week. Using QD-labeled peritoneal macrophages, we studied cell traffic during inflammation on viscera in peritoneum cavity. QD-labeled macrophages were transplanted into the peritoneum of the mouse, and colitis was induced by intracolonic injection of a hapten, trinitrobenzensulfonic acid. With the aid of stong signals of QDs, we found that macrophage accumuled on the inflammation site of the colon. These results suggested that fluorescent probes of QDs might be useful as bioimaging tools for tracing target cells in vivo.

  1. Embryo adoption: Some further considerations.

    PubMed

    Patterson, Colin

    2015-02-01

    Recent discussions of embryo adoption have sought to make sense of the teaching of the Congregation for the Doctrine of the Faith (CDF) document Dignitas personae which appeared to provide a negative judgment on such a practice. This article aims to provide a personalist account of the process of fertilization and implantation that might serve as the basis for the negative judgment of the CDF document. In doing so, it relies upon the idea that a person, including an embryo, is not to be considered in isolation, but always in relation to God and to others. This approach extends the substantialist conceptualizations commonly employed in discussions of this issue. More generally, the article seeks to highlight the value of a personalist re-framing for an understanding of the moral questions surrounding the beginning of life. Lay summary: This article seeks to make sense of what appears to be a clear-cut rejection, set out in the Congregation for the Doctrine of the Faith (CDF) document Dignitas personae, of the proposal for women to "adopt" surplus frozen embryos. It draws upon more recently developed modes of philosophical/theological reasoning to argue that, in human procreation, both fertilization and implantation represent constitutive dimensions of divine creative activity and so must be protected from manipulative technological intervention. Since embryo adoption requires this kind of technology, it makes sense for the Church document not to approve it. PMID:25698841

  2. Adoption Factors of the Electronic Health Record: A Systematic Review

    PubMed Central

    2016-01-01

    Background The Health Information Technology for Economic and Clinical Health (HITECH) was a significant piece of legislation in America that served as a catalyst for the adoption of health information technology. Following implementation of the HITECH Act, Health Information Technology (HIT) experienced broad adoption of Electronic Health Records (EHR), despite skepticism exhibited by many providers for the transition to an electronic system. A thorough review of EHR adoption facilitator and barriers provides ongoing support for the continuation of EHR implementation across various health care structures, possibly leading to a reduction in associated economic expenditures. Objective The purpose of this review is to compile a current and comprehensive list of facilitators and barriers to the adoption of the EHR in the United States. Methods Authors searched Cumulative Index of Nursing and Allied Health Literature (CINAHL) and MEDLINE, 01/01/2012–09/01/2015, core clinical/academic journals, MEDLINE full text, and evaluated only articles germane to our research objective. Team members selected a final list of articles through consensus meetings (n=31). Multiple research team members thoroughly read each article to confirm applicability and study conclusions, thereby increasing validity. Results Group members identified common facilitators and barriers associated with the EHR adoption process. In total, 25 adoption facilitators were identified in the literature occurring 109 times; the majority of which were efficiency, hospital size, quality, access to data, perceived value, and ability to transfer information. A total of 23 barriers to adoption were identified in the literature, appearing 95 times; the majority of which were cost, time consuming, perception of uselessness, transition of data, facility location, and implementation issues. Conclusions The 25 facilitators and 23 barriers to the adoption of the EHR continue to reveal a preoccupation on cost, despite

  3. Oncolytic poliovirus therapy and immunization with poliovirus-infected cell lysate induces potent antitumor immunity against neuroblastoma in vivo.

    PubMed

    Toyoda, Hidemi; Wimmer, Eckard; Cello, Jeronimo

    2011-01-01

    In a previous study, we demonstrated that neuroblastoma subcutaneously implanted in immuno-competent mice is eliminated by intratumoral administration of neuroattenuated poliovirus (PV). Our results also suggested that the in vivo destruction of neuroblastoma cells by virotherapy lead to a robust antitumor immune response. In this work, splenocytes harvested from neuroblastoma-bearing animals treated with neuroattenuated PV exhibited significantly higher lytic activity against tumor target cells than did those from splenocytes derived from control mice. In vitro T-cell depletion experiments indicated that CD8(+) T cells were essential for the cytotoxic antitumor activity of splenocytes. Moreover, adoptive transfer of splenocytes obtained from mice cured of neuroblastoma by PV virotherapy markedly delayed the tumor growth of previously established neuroblastomas in recipient naïve mice. These results confirmed that treatment with a neuroattenuated oncolytic PV strain induces antitumor immunity against neuroblastoma that is mainly mediated by cytotoxic CD8(+) T cells. Immunocompetent mice, on the other hand, were immunized with PV-infected neuroblastoma cell lysate prior intravenous challenge with neuroblastoma cells. As a control, mice were vaccinated with either non-infected neuroblastoma cell lysate alone or mixed with PV, or with PBS prior tumor cell injection. Results showed that survival is significantly prolonged only in mice immunized with PV-infected tumor lysate. This finding clearly suggested that in vitro poliovirus infection of neuroblastoma cells turns these cells into a potent tumor immunogen. Further studies in oncolytic treatment of neuroblastoma using attenuated PV alone or in combination with immunotherapy with PV oncolysate should improve the probability for successful translation in the clinic.

  4. Integrated Circuit Immunity

    NASA Technical Reports Server (NTRS)

    Sketoe, J. G.; Clark, Anthony

    2000-01-01

    This paper presents a DOD E3 program overview on integrated circuit immunity. The topics include: 1) EMI Immunity Testing; 2) Threshold Definition; 3) Bias Tee Function; 4) Bias Tee Calibration Set-Up; 5) EDM Test Figure; 6) EMI Immunity Levels; 7) NAND vs. and Gate Immunity; 8) TTL vs. LS Immunity Levels; 9) TP vs. OC Immunity Levels; 10) 7805 Volt Reg Immunity; and 11) Seventies Chip Set. This paper is presented in viewgraph form.

  5. The 17D-204 Vaccine Strain-Induced Protection against Virulent Yellow Fever Virus Is Mediated by Humoral Immunity and CD4+ but not CD8+ T Cells

    PubMed Central

    Lam, L. K. Metthew; Klimstra, William B.

    2016-01-01

    A gold standard of antiviral vaccination has been the safe and effective live-attenuated 17D-based yellow fever virus (YFV) vaccines. Among more than 500 million vaccinees, only a handful of cases have been reported in which vaccinees developed a virulent wild type YFV infection. This efficacy is presumed to be the result of both neutralizing antibodies and a robust T cell response. However, the particular immune components required for protection against YFV have never been evaluated. An understanding of the immune mechanisms that underlie 17D-based vaccine efficacy is critical to the development of next-generation vaccines against flaviviruses and other pathogens. Here we have addressed this question for the first time using a murine model of disease. Similar to humans, vaccination elicited long-term protection against challenge, characterized by high neutralizing antibody titers and a robust T cell response that formed long-lived memory. Both CD4+ and CD8+ T cells were polyfunctional and cytolytic. Adoptive transfer of immune sera or CD4+ T cells provided partial protection against YFV, but complete protection was achieved by transfer of both immune sera and CD4+ T cells. Thus, robust CD4+ T cell activity may be a critical contributor to protective immunity elicited by highly effective live attenuated vaccines. PMID:27463517

  6. The 17D-204 Vaccine Strain-Induced Protection against Virulent Yellow Fever Virus Is Mediated by Humoral Immunity and CD4+ but not CD8+ T Cells.

    PubMed

    Watson, Alan M; Lam, L K Metthew; Klimstra, William B; Ryman, Kate D

    2016-07-01

    A gold standard of antiviral vaccination has been the safe and effective live-attenuated 17D-based yellow fever virus (YFV) vaccines. Among more than 500 million vaccinees, only a handful of cases have been reported in which vaccinees developed a virulent wild type YFV infection. This efficacy is presumed to be the result of both neutralizing antibodies and a robust T cell response. However, the particular immune components required for protection against YFV have never been evaluated. An understanding of the immune mechanisms that underlie 17D-based vaccine efficacy is critical to the development of next-generation vaccines against flaviviruses and other pathogens. Here we have addressed this question for the first time using a murine model of disease. Similar to humans, vaccination elicited long-term protection against challenge, characterized by high neutralizing antibody titers and a robust T cell response that formed long-lived memory. Both CD4+ and CD8+ T cells were polyfunctional and cytolytic. Adoptive transfer of immune sera or CD4+ T cells provided partial protection against YFV, but complete protection was achieved by transfer of both immune sera and CD4+ T cells. Thus, robust CD4+ T cell activity may be a critical contributor to protective immunity elicited by highly effective live attenuated vaccines. PMID:27463517

  7. Policy Issues in Gay and Lesbian Adoption.

    ERIC Educational Resources Information Center

    Sullivan, Ann

    1995-01-01

    Notes that adoption agencies have developed few specific policies on the issue of lesbian and gay adoption. Provides an overview of key considerations about homosexual adopters, including beliefs and values of agency professionals, the legal and social ramifications of adoption into a relationship not based on marriage, and possible consequences…

  8. 18 CFR 341.6 - Adoption rule.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 18 Conservation of Power and Water Resources 1 2012-04-01 2012-04-01 false Adoption rule. 341.6... SUBJECT TO SECTION 6 OF THE INTERSTATE COMMERCE ACT § 341.6 Adoption rule. (a) Change in name of carrier... such occurrence. The filing of adoption notices and adoption supplements requires no notice period....

  9. 18 CFR 341.6 - Adoption rule.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Adoption rule. 341.6... SUBJECT TO SECTION 6 OF THE INTERSTATE COMMERCE ACT § 341.6 Adoption rule. (a) Change in name of carrier... such occurrence. The filing of adoption notices and adoption supplements requires no notice period....

  10. 18 CFR 341.6 - Adoption rule.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 18 Conservation of Power and Water Resources 1 2013-04-01 2013-04-01 false Adoption rule. 341.6... SUBJECT TO SECTION 6 OF THE INTERSTATE COMMERCE ACT § 341.6 Adoption rule. (a) Change in name of carrier... such occurrence. The filing of adoption notices and adoption supplements requires no notice period....

  11. 18 CFR 341.6 - Adoption rule.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 18 Conservation of Power and Water Resources 1 2011-04-01 2011-04-01 false Adoption rule. 341.6... SUBJECT TO SECTION 6 OF THE INTERSTATE COMMERCE ACT § 341.6 Adoption rule. (a) Change in name of carrier... such occurrence. The filing of adoption notices and adoption supplements requires no notice period....

  12. 33 CFR 230.21 - Adoption.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... FOR IMPLEMENTING NEPA § 230.21 Adoption. See 40 CFR 1506.3. A district commander will normally adopt... recirculated as provided in 40 CFR 1506.3 (b) or (c), the adopted EIS with the supplement, if any, will be processed in accordance with this regulation. A district commander may also adopt another agency's EA/FONSI....

  13. 33 CFR 230.21 - Adoption.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... FOR IMPLEMENTING NEPA § 230.21 Adoption. See 40 CFR 1506.3. A district commander will normally adopt... recirculated as provided in 40 CFR 1506.3 (b) or (c), the adopted EIS with the supplement, if any, will be processed in accordance with this regulation. A district commander may also adopt another agency's EA/FONSI....

  14. 33 CFR 230.21 - Adoption.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... FOR IMPLEMENTING NEPA § 230.21 Adoption. See 40 CFR 1506.3. A district commander will normally adopt... recirculated as provided in 40 CFR 1506.3 (b) or (c), the adopted EIS with the supplement, if any, will be processed in accordance with this regulation. A district commander may also adopt another agency's EA/FONSI....

  15. 33 CFR 230.21 - Adoption.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... FOR IMPLEMENTING NEPA § 230.21 Adoption. See 40 CFR 1506.3. A district commander will normally adopt... recirculated as provided in 40 CFR 1506.3 (b) or (c), the adopted EIS with the supplement, if any, will be processed in accordance with this regulation. A district commander may also adopt another agency's EA/FONSI....

  16. 33 CFR 230.21 - Adoption.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... FOR IMPLEMENTING NEPA § 230.21 Adoption. See 40 CFR 1506.3. A district commander will normally adopt... recirculated as provided in 40 CFR 1506.3 (b) or (c), the adopted EIS with the supplement, if any, will be processed in accordance with this regulation. A district commander may also adopt another agency's EA/FONSI....

  17. Adoption and Single Parents: A Review.

    ERIC Educational Resources Information Center

    Groze, Vic

    1991-01-01

    Examines the literature about people who choose to become single adoptive parents. Reviews the demographic and personal characteristics of single parents who adopt, and summarizes the experiences of single parents with the children they adopt. Calls for further research on single parents who adopt special needs children. (GH)

  18. Uric acid enhances the antitumor immunity of dendritic cell-based vaccine.

    PubMed

    Wang, Yihan; Ma, Xuelei; Su, Chao; Peng, Bin; Du, Jing; Jia, Hongyuan; Luo, Min; Fang, Chunju; Wei, Yuquan

    2015-01-01

    Uric acid (UA) released from dying cells has been recognized by the immune system as a danger signal. In response to UA, dendritic cells (DC) in the immune system mature and enhance the T cell response to foreign antigens. It is conceivable that the antitumor immunity of a tumor vaccine could be promoted by the administration of UA. To test this concept, we applied UA as an adjuvant to a DC-based vaccine, and discovered that the administration of UA as an adjuvant significantly enhanced the ability of the tumor lysate-pulsed DC vaccine in delaying the tumor growth. The antitumor activity was achieved with adoptively transferred lymphocytes, and both CD8(+) T cells and NK cells were required to achieve effective immunity. This resulted in an increased accumulation of activated CD8(+) T cells and an elevated production of IFN-γ. Collectively, our study shows that the administration of UA enhances the antitumor activity of tumor lysate-pulsed DC vaccine, thus providing the preclinical rationale for the application of UA in DC-based vaccine strategies.

  19. IFT20 controls LAT recruitment to the immune synapse and T-cell activation in vivo.

    PubMed

    Vivar, Omar I; Masi, Giulia; Carpier, Jean-Marie; Magalhaes, Joao G; Galgano, Donatella; Pazour, Gregory J; Amigorena, Sebastian; Hivroz, Claire; Baldari, Cosima T

    2016-01-12

    Biogenesis of the immune synapse at the interface between antigen-presenting cells and T cells assembles and organizes a large number of membrane proteins required for effective signaling through the T-cell receptor. We showed previously that the intraflagellar transport protein 20 (IFT20), a component of the intraflagellar transport system, controls polarized traffic during immune synapse assembly. To investigate the role of IFT20 in primary CD4(+) T cells in vitro and in vivo, we generated mice bearing a conditional defect of IFT20 expression in T cells. We show that in the absence of IFT20, although cell spreading and the polarization of the centrosome were unaffected, T-cell receptor (TCR)-mediated signaling and recruitment of the signaling adaptor LAT (linker for activation of T cells) at the immune synapse were reduced. As a consequence, CD4(+) T-cell activation and proliferation were also defective. In vivo, conditional IFT20-deficient mice failed to mount effective antigen-specific T-cell responses, and their T cells failed to induce colitis after adoptive transfer to Rag(-/-) mice. IFT20 is therefore required for the delivery of the intracellular pool of LAT to the immune synapse in naive primary T lymphocytes and for effective T-cell responses in vivo. PMID:26715756

  20. IFT20 controls LAT recruitment to the immune synapse and T-cell activation in vivo

    PubMed Central

    Vivar, Omar I.; Masi, Giulia; Carpier, Jean-Marie; Magalhaes, Joao G.; Galgano, Donatella; Pazour, Gregory J.; Amigorena, Sebastian; Hivroz, Claire; Baldari, Cosima T.

    2016-01-01

    Biogenesis of the immune synapse at the interface between antigen-presenting cells and T cells assembles and organizes a large number of membrane proteins required for effective signaling through the T-cell receptor. We showed previously that the intraflagellar transport protein 20 (IFT20), a component of the intraflagellar transport system, controls polarized traffic during immune synapse assembly. To investigate the role of IFT20 in primary CD4+ T cells in vitro and in vivo, we generated mice bearing a conditional defect of IFT20 expression in T cells. We show that in the absence of IFT20, although cell spreading and the polarization of the centrosome were unaffected, T-cell receptor (TCR)-mediated signaling and recruitment of the signaling adaptor LAT (linker for activation of T cells) at the immune synapse were reduced. As a consequence, CD4+ T-cell activation and proliferation were also defective. In vivo, conditional IFT20-deficient mice failed to mount effective antigen-specific T-cell responses, and their T cells failed to induce colitis after adoptive transfer to Rag−/− mice. IFT20 is therefore required for the delivery of the intracellular pool of LAT to the immune synapse in naive primary T lymphocytes and for effective T-cell responses in vivo. PMID:26715756

  1. Adopted: A practical salinity scale

    NASA Astrophysics Data System (ADS)

    The Unesco/ICES/SCOR/IAPSO Joint Panel on Oceanographic Tables and Standards has recommended the adoption of a Practical Salinity Scale, 1978, and a corresponding new International Equation of State of Seawater, 1980. A full account of the research leading to their recommendation is available in the series Unesco Technical Papers in Marine Science.The parent organizations have accepted the panel's recommendations and have set January 1, 1982, as the date when the new procedures, formulae, and tables should replace those now in use.

  2. UN adopts Law of Sea

    NASA Astrophysics Data System (ADS)

    Richman, Barbara T.

    After more than 8 years of diplomatic wrangling, the United Nations Convention on the Law of the Sea was adopted on April 30 by a vote of 130 to 4. The United States, Israel, Turkey, and Venezuela voted against the treaty; 17 nations—including the Soviet Union, West Germany, and Britain—abstained.The treaty, which would give nations the exclusive rights to natural resources in the continental shelf up to approximately 650 km offshore, will be signed in December. The treaty becomes effective 1 year after at least 60 nations ratify it.

  3. NK cells interfere with the generation of resistance against mycoplasma respiratory infection following nasal-pulmonary immunization1

    PubMed Central

    Bodhankar, Sheetal; Woolard, Mathew D.; Sun, Xiangle; Simecka, Jerry W.

    2009-01-01

    The purpose of the present study was to determine the impact of NK cells on the development of protective adaptive immunity in response to nasal-pulmonary immunization against mycoplasma. Depletion of NK cells prior to nasal-pulmonary immunization enhanced resistance to mycoplasma respiratory infection. The effect of NK cells on the generation of protective immunity in lungs was dependent on lymphoid cells, as immunization of either SCID mice or immunocompetent mice depleted of CD4+ T cells did not demonstrate any increased resistance in the presence or absence of NK cells. The presence of NK cells at the time of nasal-pulmonary immunization modulated mycoplasma-specific cytokine responses in lungs and lower respiratory nodes. In particular, NK cells skewed the mycoplasma-specific T cell cytokine responses in the draining lymph nodes to higher IL-4, IL-13 and IL-17 while lowering IFN-γ responses. Adoptive transfer of total lung lymphocytes isolated from immunized mice into naïve mice led to a significant reduction in the mycoplasma numbers in lungs, and the resistance was greater if cells were obtained from immunized mice which were depleted of NK cells. Similar results were obtained if purified B cells, T cells or CD4+ T cells were used. Interestingly, this is the first time that a favorable role of functional CD4+ T cells in mediating protection in mycoplasma respiratory disease was demonstrated. Thus, NK cells can influence the responses of multiple lymphocyte populations capable of mediating resistance to mycoplasma infection. PMID:19625649

  4. Governmental Immunity: Legal Basis and Implications for Public Education.

    ERIC Educational Resources Information Center

    Connors, Eugene T.

    The concept of sovereign immunity in English law originated in both early canon law and the feudal system, became formalized in case law under King Henry II, and as the royal prerogative, became established into statutory law under King Henry VIII. This concept of governmental immunity was adopted by the states when the union was founded. The case…

  5. 78 FR 60877 - Advisory Committee on Immunization Practices (ACIP)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-02

    ... HUMAN SERVICES Centers for Disease Control and Prevention Advisory Committee on Immunization Practices... of the Public Health Service Act, immunization recommendations of the ACIP that have been adopted by... plans. Matters To Be Discussed: The agenda will include discussions on: child/adolescent...

  6. [Adoptive parents' satisfaction with the adoption experience and with its impact on family life].

    PubMed

    Sánchez-Sandoval, Yolanda

    2011-11-01

    In this study, we discuss the relevance of adoptive families' satisfaction in the assessment of adoption processes. The effects of adoption on a sample group of 272 adoptive families are analyzed. Most families show high levels of satisfaction as to: their decision to adopt, the features of their adopted children and how adoption has affected them as individuals and as a family. Statistical analyses show that these families can have different satisfaction levels depending on certain features of the adoptees, of the adoptive families or of their educational style. Life satisfaction of the adoptees is also related to how their adoptive parents evaluate the adoption.

  7. [Adoptive parents' satisfaction with the adoption experience and with its impact on family life].

    PubMed

    Sánchez-Sandoval, Yolanda

    2011-11-01

    In this study, we discuss the relevance of adoptive families' satisfaction in the assessment of adoption processes. The effects of adoption on a sample group of 272 adoptive families are analyzed. Most families show high levels of satisfaction as to: their decision to adopt, the features of their adopted children and how adoption has affected them as individuals and as a family. Statistical analyses show that these families can have different satisfaction levels depending on certain features of the adoptees, of the adoptive families or of their educational style. Life satisfaction of the adoptees is also related to how their adoptive parents evaluate the adoption. PMID:22047850

  8. T-cell-dependent immunity and thrombocytopenia in rats infected with Plasmodium chabaudi.

    PubMed Central

    Watier, H; Verwaerde, C; Landau, I; Werner, E; Fontaine, J; Capron, A; Auriault, C

    1992-01-01

    Normal, splenectomized, and athymic Fischer rats were infected with Plasmodium chabaudi. In normal rat infections, acute-phase infection resolved rapidly and completely. In splenectomized rats, infection resulted in high parasitemia and ultimately death. In nude rats, parasite growth was reduced compared with normal rats, and a persistent parasitemia (between 20 and 45%) was observed for several months. Complete resolution of the infection was achieved after adoptive transfer of T lymphocytes, even when transfer occurred during the course of infection. These results indicated that an acquired, T-lymphocyte-dependent immunity was necessary for the complete recovery observed in normal rats. In normal rats, thrombocytopenia and splenomegaly occurred during infection. By contrast, in nude rats, both of these pathological manifestations were only observed after thymus grafting. Thrombocytopenia was also absent in the splenectomized animals. Despite an increase in platelet-associated immunoglobulin levels during the infection, thrombocytopenia was not transferred by injection of infected rat serum to normal recipients. It has been concluded that the nude rat infection can be regarded as a novel and useful model for studying the T-cell-dependent effector and pathological mechanisms and to investigate the anti-P. chabaudi immune response. PMID:1729178

  9. Embryo adoption: Some further considerations

    PubMed Central

    Patterson, Colin

    2015-01-01

    Recent discussions of embryo adoption have sought to make sense of the teaching of the Congregation for the Doctrine of the Faith (CDF) document Dignitas personae which appeared to provide a negative judgment on such a practice. This article aims to provide a personalist account of the process of fertilization and implantation that might serve as the basis for the negative judgment of the CDF document. In doing so, it relies upon the idea that a person, including an embryo, is not to be considered in isolation, but always in relation to God and to others. This approach extends the substantialist conceptualizations commonly employed in discussions of this issue. More generally, the article seeks to highlight the value of a personalist re-framing for an understanding of the moral questions surrounding the beginning of life. Lay summary: This article seeks to make sense of what appears to be a clear-cut rejection, set out in the Congregation for the Doctrine of the Faith (CDF) document Dignitas personae, of the proposal for women to “adopt” surplus frozen embryos. It draws upon more recently developed modes of philosophical/theological reasoning to argue that, in human procreation, both fertilization and implantation represent constitutive dimensions of divine creative activity and so must be protected from manipulative technological intervention. Since embryo adoption requires this kind of technology, it makes sense for the Church document not to approve it. PMID:25698841

  10. Universal varicella vaccine immunization in Japan.

    PubMed

    Yoshikawa, Tetsushi; Kawamura, Yoshiki; Ohashi, Masahiro

    2016-04-01

    In 1974, Japanese scientists developed a live attenuated varicella vaccine based on the Oka strain. The efficacy of the vaccine for the prevention of varicella has been primarily demonstrated in studies conducted in the United States following the adoption of universal immunization using the Oka strain varicella vaccine in 1996. Although the vaccine was developed by Japanese scientists, until recently, the vaccine has been administered on a voluntary basis in Japan resulting in a vaccine coverage rate of approximately 40%. Therefore, Japan initiated universal immunization using the Oka strain varicella vaccine in November 2014. Given the transition from voluntary to universal immunization in Japan, it will also be important to monitor the epidemiology of varicella and herpes zoster. The efficacy and safety of co-administration of the varicella vaccine and measles, mumps, and rubella vaccine have been demonstrated in many countries; however, there was no data from Japan. In order to adopt the practice of universal immunization using the Oka strain varicella vaccine in Japan, data demonstrating the efficacy and safety of co-administration of varicella vaccine and measles and rubella (MR) vaccine were required. Additionally, we needed to elucidate the appropriate time interval between the first and second administrations of the vaccine. It is also important to differentiate between wild type and Oka vaccine type strains in herpes zoster patient with past history of varicella vaccine. Thus, there are many factors to consider regarding the adoption of universal immunization in Japan to control varicella zoster virus (VZV) infections.

  11. HLA ligandome analysis identifies the underlying specificities of spontaneous antileukemia immune responses in chronic lymphocytic leukemia (CLL)

    PubMed Central

    Kowalewski, Daniel J.; Schuster, Heiko; Backert, Linus; Berlin, Claudia; Kahn, Stefan; Kanz, Lothar; Salih, Helmut R.; Rammensee, Hans-Georg; Stevanovic, Stefan; Stickel, Juliane Sarah

    2015-01-01

    The breakthrough development of clinically effective immune checkpoint inhibitors illustrates the potential of T-cell–based immunotherapy to effectively treat malignancies. A remaining challenge is to increase and guide the specificities of anticancer immune responses, e.g., by therapeutic vaccination or by adoptive T-cell transfer. By analyzing the landscape of naturally presented HLA class I and II ligands of primary chronic lymphocytic leukemia (CLL), we delineated a novel category of tumor-associated T-cell antigens based on their exclusive and frequent representation in the HLA ligandome of leukemic cells. These antigens were validated across different stages and mutational subtypes of CLL and found to be robustly represented in HLA ligandomes of patients undergoing standard chemo-/immunotherapy. We demonstrate specific immune recognition of these antigens exclusively in CLL patients, with the frequencies of representation in CLL ligandomes correlating with the frequencies of immune recognition by patient T cells. Moreover, retrospective survival analysis revealed survival benefits for patients displaying immune responses to these antigens. These results directly imply these nonmutant self-peptides as pathophysiologically relevant tumor antigens and encourages their implementation for cancer immunotherapy. PMID:25548167

  12. The exosomes in tumor immunity

    PubMed Central

    Liu, Yanfang; Gu, Yan; Cao, Xuetao

    2015-01-01

    Exosomes are a kind of nanometric membrane vesicles and can be released by almost all kinds of cells, including cancer cells. As the important mediators in intercellular communications, exosomes mediate exchange of protein and genetic material derived from parental cells. Emerging evidences show that exosomes secreted by either host cells or cancer cells are involved in tumor initiation, growth, invasion and metastasis. Moreover, communications between immune cells and cancer cells via exosomes play dual roles in modulating tumor immunity. In this review, we focus on exosome-mediated immunosuppression via inhibition of antitumor responses elicited by immune cells (DCs, NK cells, CD4+ and CD8+ T cells, etc.) and induction of immunosuppressive or regulatory cell populations (MDSCs, Tregs and Bregs). Transfer of cytokines, microRNAs (miRNAs) and functional mRNAs by tumor-derived exosomes (TEXs) is crucial in the immune escape. Furthermore, exosomes secreted from several kinds of immune cells (DCs, CD4+ and CD8+ Tregs) also participate in immunosuppression. On the other hand, we summarize the current application of DC-derived and modified tumor-derived exosomes as tumor vaccines. The potential challenges about exosome-based vaccines for clinical application are also discussed. PMID:26405598

  13. HUMAN IMMUNITY TO THE MENINGOCOCCUS

    PubMed Central

    Goldschneider, Irving; Gotschlich, Emil C.; Artenstein, Malcolm S.

    1969-01-01

    Results of the present study suggest that natural immunity to meningococcal disease is initiated, reinforced, and broadened by intermittent carriage of different strains of meningococci throughout life. In young adults, carriage of meningococci in the nasopharynx is an efficient process of immune sensitization. 92% of carriers of serogroup B, C, or Bo meningococci were found to develop increased titers of serum bactericidal activity to their own meningococcal isolate, and 87% developed bactericidal activity to heterologous strains of pathogenic meningococci. The rise in bactericidal titer occurred within 2 wk of onset of the carrier state, and was accompanied by an increase in titer of specific IgG, IgM, and IgA antibodies to meningococci. In early childhood, when few children have antibodies to pathogenic meningococci, active immunization seems to occur as a result of carriage of atypical, nonpathogenic strains. Immunity to systemic meningococcal infection among infants in the neonatal period is associated with the passive transfer of IgG antibodies from mother to fetus. The antigenic determinants which initiate the immune response to meningococci include the group-specific C polysaccharide, cross-reactive antigens, and type-specific antigens. PMID:4977281

  14. Immunity and immunization in elderly.

    PubMed

    Bourée, Patrice

    2003-12-01

    As the average life expectancy increases, retired people want to travel. Five to 8% of travellers in tropical areas are old persons. Immune system suffers of old age as the other organs. The number and the functions of the T-lymphocytes decrease, but the B-lymphocytes are not altered. So, the response to the vaccinations is slower and lower in the elderly. Influenza is a great cause of death rate in old people. The seroconversion, after vaccine, is 50% from 60 to 70 years old, 31% from 70 to 80 years old, and only 11% after 80 years old. But in public health, the vaccination reduced the morbidity by 25%, admission to hospital by 20%, pneumonia by 50%, and mortality by 70%. Antipoliomyelitis vaccine is useful for travellers, as the vaccines against hepatitis and typhoid fever. Pneumococcal vaccine is effective in 60%. Tetanus is fatal in at last 32% of the people above 80 years, therefore this vaccine is very important.

  15. Effect of feeding whole compared with cell-free colostrum on calf immune status: Vaccination response.

    PubMed

    Langel, S N; Wark, W A; Garst, S N; James, R E; McGilliard, M L; Petersson-Wolfe, C S; Kanevsky-Mullarky, I

    2016-05-01

    Vaccination contributes to improved herd health and production. Boosting immune development at a young age may have long-term effects by enhancing vaccine immune response and efficacy. In the bovine, colostrum is the sole source of maternal immunity, having a substantial effect on health status in the neonate. To date, colostral antibody concentration is used to evaluate colostrum quality. However, colostrum also contains proteins and cells, which may affect immune development and future responses to vaccines. To determine the effect of maternal colostral cells on immune development, 37 female Holstein and Jersey dairy calves were bottle-fed 4 quarts total of whole colostrum (WC) or cell-free colostrum (CFC) at birth. Calves were vaccinated with 2 series of multivalent vaccines. Series A consisted of vaccines given between 1 and 4mo of life. Series B consisted of vaccines given between 5 and 10mo of life. Calf peripheral blood samples were obtained before each vaccination series and monthly for 3mo after each vaccination series. Cellular blood parameters were determined by flow cytometry. Quantitative real-time PCR was used to determine cytokine gene expression in peripheral blood mononuclear cells before vaccination series B and once a month for 2mo after vaccination series B. Calves fed CFC had fewer numbers of B cells in mo 2 after vaccination series A when compared with WC-fed calves. Calves fed CFC had decreased gene expression levels of IL-2 in mo 1 and numbers of CD4(+)CD62L(+)CD45RO(-) and CD4(+)CD62L(+)CD45RO(+) T cells in mo 0 and 1 after vaccination series B as compared with WC-fed calves. Our findings indicate a greater response to vaccines up to 6 to 10mo post-WC feeding when compared with CFC. These data suggest that adoptive transfer of maternal colostral cells at birth has a long-term effect on development of the neonatal immune system. PMID:26923041

  16. Effect of feeding whole compared with cell-free colostrum on calf immune status: Vaccination response.

    PubMed

    Langel, S N; Wark, W A; Garst, S N; James, R E; McGilliard, M L; Petersson-Wolfe, C S; Kanevsky-Mullarky, I

    2016-05-01

    Vaccination contributes to improved herd health and production. Boosting immune development at a young age may have long-term effects by enhancing vaccine immune response and efficacy. In the bovine, colostrum is the sole source of maternal immunity, having a substantial effect on health status in the neonate. To date, colostral antibody concentration is used to evaluate colostrum quality. However, colostrum also contains proteins and cells, which may affect immune development and future responses to vaccines. To determine the effect of maternal colostral cells on immune development, 37 female Holstein and Jersey dairy calves were bottle-fed 4 quarts total of whole colostrum (WC) or cell-free colostrum (CFC) at birth. Calves were vaccinated with 2 series of multivalent vaccines. Series A consisted of vaccines given between 1 and 4mo of life. Series B consisted of vaccines given between 5 and 10mo of life. Calf peripheral blood samples were obtained before each vaccination series and monthly for 3mo after each vaccination series. Cellular blood parameters were determined by flow cytometry. Quantitative real-time PCR was used to determine cytokine gene expression in peripheral blood mononuclear cells before vaccination series B and once a month for 2mo after vaccination series B. Calves fed CFC had fewer numbers of B cells in mo 2 after vaccination series A when compared with WC-fed calves. Calves fed CFC had decreased gene expression levels of IL-2 in mo 1 and numbers of CD4(+)CD62L(+)CD45RO(-) and CD4(+)CD62L(+)CD45RO(+) T cells in mo 0 and 1 after vaccination series B as compared with WC-fed calves. Our findings indicate a greater response to vaccines up to 6 to 10mo post-WC feeding when compared with CFC. These data suggest that adoptive transfer of maternal colostral cells at birth has a long-term effect on development of the neonatal immune system.

  17. Immune System Involvement

    MedlinePlus

    ... Tips" to find out more! Email * Zipcode The Immune System and Psoriatic Disease What is an autoimmune disease? ... swollen and painful joints and tendons. Treating the immune system The immune system is not only the key ...

  18. Immunization and Pregnancy

    MedlinePlus

    Immunization & Pregnancy Vaccines help keep apregnant woman and her growing family healthy. Vaccine Before pregnancy Hepatitis A ... 232-4636) • English or Spanish National Center for Immunization and Respiratory Diseases Immunization Services Division CS238938B 03/ ...

  19. Childhood Immunization Schedule

    MedlinePlus

    ... Recommendations Why Immunize? Vaccines: The Basics Instant Childhood Immunization Schedule Recommend on Facebook Tweet Share Compartir Get ... date. See Disclaimer for additional details. Based on Immunization Schedule for Children 0 through 6 Years of ...

  20. [Adoption: an alternative to assisted reproductive techniques?].

    PubMed

    Blanchy, S

    2011-09-01

    Information on adoption must be given to couples who seek treatment for medically-assisted procreation. But is adoption a real alternative? What are the chances for a couple who consults to see its desire for adoption be achieved according to its own situation, the characteristics of the child he wants, and the general situation of adoption? Can adoption, just like assisted procreation, often described by the couples as a "obstacle course", go parallel? Or should one try adoption once assisted reproduction failed? Is the couple willing to suffer the social and legal control of adoption after having supported the medical control of the ART? In all cases, the reality is that two out of three couples engaged in assisted reproduction will have a child whereas scarcely more than one candidate to adoption will be offered to adopt a child after three or four-years procedure.

  1. Electronic Dental Records System Adoption.

    PubMed

    Abramovicz-Finkelsztain, Renata; Barsottini, Claudia G N; Marin, Heimar Fatima

    2015-01-01

    The use of Electronic Dental Records (EDRs) and management software has become more frequent, following the increase in prevelance of new technologies and computers in dental offices. The purpose of this study is to identify and evaluate the use of EDRs by the dental community in the São Paulo city area. A quantitative case study was performed using a survey on the phone. A total of 54 offices were contacted and only one declinedparticipation in this study. Only one office did not have a computer. EDRs were used in 28 offices and only four were paperless. The lack of studies in this area suggests the need for more usability and implementation studies on EDRs so that we can improve EDR adoption by the dental community.

  2. Autochthonous primary and metastatic melanomas in Hgf-Cdk4 R24C mice evade T-cell-mediated immune surveillance.

    PubMed

    Landsberg, Jennifer; Gaffal, Evelyn; Cron, Mira; Kohlmeyer, Judith; Renn, Marcel; Tüting, Thomas

    2010-10-01

    Genetically engineered mouse models offer new opportunities to investigate the role of cell-mediated immunity in the natural progression of melanoma in an immunocompetent host. Here we report that Hgf-Cdk4(R24C) mice spontaneously develop a spectrum of primary melanomas with high penetrance during their first year of life. Malignant transformation proceeds in a stepwise manner from multiple melanocytic nevi to single nodular melanomas and disseminated metastases in most mice. Migrating melanoma cells invade the draining lymph nodes without activating the immune system. Autochthonous primary tumors are destroyed following experimental introduction of immune surveillance using an adoptive lymphocyte transfer approach. However, some tumor cells are able to survive, evade immune cell control, and recur both locally and systemically. Immune tolerance in recurring tumors may be supported by immunosuppressive Gr1(+) myeloid cells. Taken together, our results demonstrate that primary and metastatic melanomas developing spontaneously in Hgf-Cdk4(R24C) mice effectively evade cellular immune surveillance. PMID:20649939

  3. Adoption of Children with Disabilities: An Exploration of the Issues for Adoptive Families

    ERIC Educational Resources Information Center

    Good, Gretchen A.

    2016-01-01

    This systematic literature review is an exploration of issues for adoptive families throughout the adoption process and into the various phases of the life of the adoptive family. Although there has been much recent research related to adoption, in general, very little adoption literature addresses the often unspoken needs of families who want to…

  4. In Their Own Words: Adopted Persons' Experiences of Adoption Disclosure and Discussion in Their Families

    ERIC Educational Resources Information Center

    Wydra, Maria; O'Brien, Karen M.; Merson, Erica S.

    2012-01-01

    This study explored adoption disclosure in a sample of 18 adult adoptees who were adopted as infants. A qualitative analysis of semistructured interviews with adoptees was used to learn about participants' experiences of adoption disclosure. The majority always knew they were adopted, were able to talk openly with parents about adoption, and had…

  5. Sovereign Immunity in a Constitutional Government: The Federal Employment Discrimination Cases

    ERIC Educational Resources Information Center

    Abernathy, Charles F.

    1975-01-01

    Considers employment discrimination suits against federal officers where application of the sovereign immunity doctrine has generated considerable confusion and attendant injustice, and develops the separation of powers rationale for sovereign immunity, showing how the immunity principles adopted by the Supreme Court implicitly define the…

  6. Adoptive T-cell Immunotherapy

    PubMed Central

    Gottschalk, Stephen; Rooney, Cliona

    2015-01-01

    Epstein-Barr virus (EBV) is associated with a range of malignancies involving B-cells, T-cells, natural killer (NK)-cells, epithelial cells and smooth muscle. All of these are associated with the latent life cycles of EBV, but the pattern of latency-associated viral antigens expressed in tumor cells depends on the type of tumor. EBV-specific T cells (EBVSTs) have been explored as prophylaxis and therapy for EBV-associated malignancies for more than two decades. EBVSTs have been most successful as prophylaxis and therapy for post-transplant lymphoproliferative disease (PTLD), which expresses the full array of latent EBV antigens (type 3 latency), in hematopoietic stem cell transplant recipients. While less effective, clinical studies have also demonstrated their therapeutic potential for PTLD post solid organ transplant, and for EBV-associated malignancies such as Hodgkin’s Lymphoma, Non-Hodgkin’s Lymphoma, and nasopharyngeal carcinoma that express a limited array of latent EBV antigens (type 2 latency),. Several approaches are actively being pursued to improve the antitumor activity of EBVSTs including activation and expansion of T cells specific for the EBV antigens expressed in type 2 latency, genetic approaches to render EBVSTs resistant to the immunosuppressive tumor environment and combination approaches with other immune-modulating modalities. Given the recent advances and renewed interest in cell therapy, we hope that EBVSTs will become an integral part of our treatment armamentarium against EBV-positive malignancies in the near future. PMID:26428384

  7. Impact of Adoption on Birth Parents

    MedlinePlus

    ... This relationship, as well as the birth parent’s perception of his or her identity, may change over ... McRoy, R. G., & Grotevant, H. D. (2000). Birthmother perceptions of the psychologically present adopted child: Adoption openness ...

  8. When to Tell Your Child About Adoption

    MedlinePlus

    ... adopted youngsters need to be told about their origins, ideally even before middle childhood. Introducing the Information ... needs to have an honest understanding of his origin. Adopted children who have not been told seem ...

  9. National Foster Care and Adoption Directory Search

    MedlinePlus

    ... on the Placement of Children (ICPC) Administrator - Provides legal and fiscal oversight for ICPC, which regulates the interstate movement of children in foster care, adoption, residential treatment, or juvenile justice programs. This person should be contacted by adoption ...

  10. The Place of Genetic Counselling in Adoption.

    ERIC Educational Resources Information Center

    Hockey, Athel; Bain, Jill

    1982-01-01

    An approach combining social worker and geneticist expertise in adoption is outlined in the study involving 180 families. Genetic counseling has shown to be an essential safeguard to the preservation of the adoptive family unit. (Author/SW)

  11. Macro influencers of electronic health records adoption.

    PubMed

    Raghavan, Vijay V; Chinta, Ravi; Zhirkin, Nikita

    2015-01-01

    While adoption rates for electronic health records (EHRs) have improved, the reasons for significant geographical differences in EHR adoption within the USA have remained unclear. To understand the reasons for these variations across states, we have compiled from secondary sources a profile of different states within the USA, based on macroeconomic and macro health-environment factors. Regression analyses were performed using these indicator factors on EHR adoption. The results showed that internet usage and literacy are significantly associated with certain measures of EHR adoption. Income level was not significantly associated with EHR adoption. Per capita patient days (a proxy for healthcare need intensity within a state) is negatively correlated with EHR adoption rate. Health insurance coverage is positively correlated with EHR adoption rate. Older physicians (>60 years) tend to adopt EHR systems less than their younger counterparts. These findings have policy implications on formulating regionally focused incentive programs.

  12. CD4+ T-Cell-Mediated Antiviral Protection of the Upper Respiratory Tract in BALB/c Mice following Parenteral Immunization with a Recombinant Respiratory Syncytial Virus G Protein Fragment

    PubMed Central

    Plotnicky-Gilquin, Hélène; Robert, Alain; Chevalet, Laurent; Haeuw, Jean-Francois; Beck, Alain; Bonnefoy, Jean-Yves; Brandt, Christian; Siegrist, Claire-Anne; Nguyen, Thien Ngoc; Power, Ultan F.

    2000-01-01

    We analyzed the protective mechanisms induced against respiratory syncytial virus subgroup A (RSV-A) infection in the lower and upper respiratory tracts (LRT and URT) of BALB/c mice after intraperitoneal immunization with a recombinant fusion protein incorporating residues 130 to 230 of RSV-A G protein (BBG2Na). Mother-to-offspring antibody (Ab) transfer and adoptive transfer of BBG2Na-primed B cells into SCID mice demonstrated that Abs are important for LRT protection but have no effect on URT infection. In contrast, RSV-A clearance in the URT was achieved in a dose-dependent fashion after adoptive transfer of BBG2Na-primed T cells, while it was abolished in BBG2Na-immunized mice upon in vivo depletion of CD4+, but not CD8+, T cells. Furthermore, the conserved RSV-A G protein cysteines and residues 193 and 194, overlapping the recently identified T helper cell epitope on the G protein (P. W. Tebbey et al., J. Exp. Med. 188:1967–1972, 1998), were found to be essential for URT but not LRT protection. Taken together, these results demonstrate for the first time that CD4+ T cells induced upon parenteral immunization with an RSV G protein fragment play a critical role in URT protection of normal mice against RSV infection. PMID:10729118

  13. Cancer treatment by photodynamic therapy combined with NK-cell-line-based adoptive immunotherapy

    NASA Astrophysics Data System (ADS)

    Korbelik, Mladen; Sun, Jinghai

    1998-05-01

    Treatment of solid cancers by photodynamic therapy (PDT) triggers a strong acute inflammatory reaction localized to the illuminated malignant tissue. This event is regulated by a massive release of various potent mediators which have a profound effect not only on local host cell populations, but also attract different types of immune cells to the treated tumor. Phagocytosis of PDT-damaged cancerous cells by antigen presenting cells, such as activated tumor associated macrophages, enables the recognition of even poorly immunogenic tumors by specific immune effector cells and the generation of immune memory populations. Because of its inflammatory/immune character, PDT is exceptionally responsive to adjuvant treatments with various types of immunotherapy. Combining PDT with immuneactivators, such as cytokines or other specific or non-specific immune agents, rendered marked improvements in tumor cures with various cancer models. Another clinically attractive strategy is adoptive immunotherapy, and the prospects of its use in conjunction with PDT are outlined.

  14. Evolution of adaptive immunity from transposable elements combined with innate immune systems.

    PubMed

    Koonin, Eugene V; Krupovic, Mart

    2015-03-01

    Adaptive immune systems in prokaryotes and animals give rise to long-term memory through modification of specific genomic loci, such as by insertion of foreign (viral or plasmid) DNA fragments into clustered regularly interspaced short palindromic repeat (CRISPR) loci in prokaryotes and by V(D)J recombination of immunoglobulin genes in vertebrates. Strikingly, recombinases derived from unrelated mobile genetic elements have essential roles in both prokaryotic and vertebrate adaptive immune systems. Mobile elements, which are ubiquitous in cellular life forms, provide the only known, naturally evolved tools for genome engineering that are successfully adopted by both innate immune systems and genome-editing technologies. In this Opinion article, we present a general scenario for the origin of adaptive immunity from mobile elements and innate immune systems.

  15. Recent advances in understanding antitumor immunity

    PubMed Central

    Munhoz, Rodrigo Ramella; Postow, Michael Andrew

    2016-01-01

    The term “antitumor immunity” refers to innate and adaptive immune responses which lead to tumor control. Turning the immune system into a destructive force against tumors has been achieved in a broad range of human cancers with the use of non-specific immunotherapies, vaccines, adoptive-cell therapy, and, more recently with significant success, through blockade of immune checkpoints. Nevertheless, the efficacy of these approaches is not universal, and tools to identify long-term responders and primarily refractory patients are warranted. In this article, we review recent advances in understanding the complex mechanisms of antitumor immunity and how these developments can be used to address open questions in a setting of growing clinical indications for the use of immunotherapy. PMID:27803807

  16. A Narrative Inquiry of International Adoption Stories

    ERIC Educational Resources Information Center

    Pryor, Christin; Pettinelli, J. Douglas

    2011-01-01

    The international adoption entrance story is an unexplored topic in the adoption literature. The stories that families tell of beginning life with their new children has important implications for the development of an autobiographical narrative of an adopted child. A coherent autobiographical narrative is vital for healthy childhood development.…

  17. 32 CFR 584.4 - Adoption proceedings.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 3 2012-07-01 2009-07-01 true Adoption proceedings. 584.4 Section 584.4... CUSTODY, AND PATERNITY § 584.4 Adoption proceedings. (a) General. This chapter does not apply to those... normally may not be put up for adoption without the consent of the parents. Therefore, communications...

  18. 25 CFR 75.18 - Adoption.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 25 Indians 1 2014-04-01 2014-04-01 false Adoption. 75.18 Section 75.18 Indians BUREAU OF INDIAN... OF CHEROKEE INDIANS, NORTH CAROLINA § 75.18 Adoption. The Tribal Council of the Eastern Band of Cherokee Indians shall be empowered to enact ordinances governing the adoption of new members....

  19. 40 CFR 1506.3 - Adoption.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 33 2011-07-01 2011-07-01 false Adoption. 1506.3 Section 1506.3 Protection of Environment COUNCIL ON ENVIRONMENTAL QUALITY OTHER REQUIREMENTS OF NEPA § 1506.3 Adoption. (a) An agency may adopt a Federal draft or final environmental impact statement or portion...

  20. 40 CFR 1506.3 - Adoption.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 32 2010-07-01 2010-07-01 false Adoption. 1506.3 Section 1506.3 Protection of Environment COUNCIL ON ENVIRONMENTAL QUALITY OTHER REQUIREMENTS OF NEPA § 1506.3 Adoption. (a) An agency may adopt a Federal draft or final environmental impact statement or portion...

  1. 32 CFR 584.4 - Adoption proceedings.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 3 2013-07-01 2013-07-01 false Adoption proceedings. 584.4 Section 584.4... CUSTODY, AND PATERNITY § 584.4 Adoption proceedings. (a) General. This chapter does not apply to those... normally may not be put up for adoption without the consent of the parents. Therefore, communications...

  2. 47 CFR 61.171 - Adoption notice.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 3 2013-10-01 2013-10-01 false Adoption notice. 61.171 Section 61.171 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES (CONTINUED) TARIFFS Adoption of Tariffs and Other Documents of Predecessor Carriers § 61.171 Adoption notice. When a...

  3. 25 CFR 75.18 - Adoption.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Adoption. 75.18 Section 75.18 Indians BUREAU OF INDIAN... OF CHEROKEE INDIANS, NORTH CAROLINA § 75.18 Adoption. The Tribal Council of the Eastern Band of Cherokee Indians shall be empowered to enact ordinances governing the adoption of new members....

  4. 47 CFR 61.171 - Adoption notice.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 3 2010-10-01 2010-10-01 false Adoption notice. 61.171 Section 61.171 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES (CONTINUED) TARIFFS Adoption of Tariffs and Other Documents of Predecessor Carriers § 61.171 Adoption notice. When a...

  5. 40 CFR 1506.3 - Adoption.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 34 2012-07-01 2012-07-01 false Adoption. 1506.3 Section 1506.3 Protection of Environment COUNCIL ON ENVIRONMENTAL QUALITY OTHER REQUIREMENTS OF NEPA § 1506.3 Adoption. (a) An agency may adopt a Federal draft or final environmental impact statement or portion...

  6. 40 CFR 1506.3 - Adoption.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 34 2013-07-01 2013-07-01 false Adoption. 1506.3 Section 1506.3 Protection of Environment COUNCIL ON ENVIRONMENTAL QUALITY OTHER REQUIREMENTS OF NEPA § 1506.3 Adoption. (a) An agency may adopt a Federal draft or final environmental impact statement or portion...

  7. 32 CFR 584.4 - Adoption proceedings.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 3 2014-07-01 2014-07-01 false Adoption proceedings. 584.4 Section 584.4... CUSTODY, AND PATERNITY § 584.4 Adoption proceedings. (a) General. This chapter does not apply to those... normally may not be put up for adoption without the consent of the parents. Therefore, communications...

  8. 47 CFR 61.171 - Adoption notice.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 3 2012-10-01 2012-10-01 false Adoption notice. 61.171 Section 61.171 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES (CONTINUED) TARIFFS Adoption of Tariffs and Other Documents of Predecessor Carriers § 61.171 Adoption notice. When a...

  9. 40 CFR 1506.3 - Adoption.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 33 2014-07-01 2014-07-01 false Adoption. 1506.3 Section 1506.3 Protection of Environment COUNCIL ON ENVIRONMENTAL QUALITY OTHER REQUIREMENTS OF NEPA § 1506.3 Adoption. (a) An agency may adopt a Federal draft or final environmental impact statement or portion...

  10. 32 CFR 584.4 - Adoption proceedings.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 3 2011-07-01 2009-07-01 true Adoption proceedings. 584.4 Section 584.4... CUSTODY, AND PATERNITY § 584.4 Adoption proceedings. (a) General. This chapter does not apply to those... normally may not be put up for adoption without the consent of the parents. Therefore, communications...

  11. 47 CFR 61.171 - Adoption notice.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 3 2011-10-01 2011-10-01 false Adoption notice. 61.171 Section 61.171 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES (CONTINUED) TARIFFS Adoption of Tariffs and Other Documents of Predecessor Carriers § 61.171 Adoption notice. When a...

  12. 25 CFR 75.18 - Adoption.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 25 Indians 1 2013-04-01 2013-04-01 false Adoption. 75.18 Section 75.18 Indians BUREAU OF INDIAN... OF CHEROKEE INDIANS, NORTH CAROLINA § 75.18 Adoption. The Tribal Council of the Eastern Band of Cherokee Indians shall be empowered to enact ordinances governing the adoption of new members....

  13. 47 CFR 61.171 - Adoption notice.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 3 2014-10-01 2014-10-01 false Adoption notice. 61.171 Section 61.171 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES (CONTINUED) TARIFFS Adoption of Tariffs and Other Documents of Predecessor Carriers § 61.171 Adoption notice. When a...

  14. 25 CFR 75.18 - Adoption.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 25 Indians 1 2011-04-01 2011-04-01 false Adoption. 75.18 Section 75.18 Indians BUREAU OF INDIAN... OF CHEROKEE INDIANS, NORTH CAROLINA § 75.18 Adoption. The Tribal Council of the Eastern Band of Cherokee Indians shall be empowered to enact ordinances governing the adoption of new members....

  15. 25 CFR 75.18 - Adoption.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 25 Indians 1 2012-04-01 2011-04-01 true Adoption. 75.18 Section 75.18 Indians BUREAU OF INDIAN... OF CHEROKEE INDIANS, NORTH CAROLINA § 75.18 Adoption. The Tribal Council of the Eastern Band of Cherokee Indians shall be empowered to enact ordinances governing the adoption of new members....

  16. International Adoption: Current Status and Future Prospects.

    ERIC Educational Resources Information Center

    Bartholet, Elizabeth

    1993-01-01

    Laws regulating adoption are varied and complex in countries that offer children for international adoption (IA), while United States Immigration laws pose additional obstacles to Americans wishing to adopt foreign-born children. Declarations by the United Nations and the development of a convention on IA by the Hague Conference offer some hope…

  17. The Adopted Adolescent. Selected Papers Number 55.

    ERIC Educational Resources Information Center

    Banning, Anne

    This review of studies on clinical and nonclinical populations explores outcomes of adoption and developmental issues for adolescents, and in particular, developmental problems for adopted adolescents. Studies on nonclinical populations demonstrate that adoption is a highly successful form of substitute care. Prospective longitudinal studies show…

  18. Adoption Bibliography and Multi-Ethnic Sourcebook.

    ERIC Educational Resources Information Center

    Van Why, Elizabeth Wharton, Comp.

    Designed for parents who have adopted or who contemplate adoption, and for educational, legal, medical, social, and theological professionals, this bibliography and source book contains over 1250 citations relating to adoption. The book is divided into two parts. The first section is a bibliography of articles, personal narratives, dissertations,…

  19. Therapeutic effects of stress-programmed lymphocytes transferred to chronically stressed mice.

    PubMed

    Scheinert, Rachel B; Haeri, Mitra H; Lehmann, Michael L; Herkenham, Miles

    2016-10-01

    Our group has recently provided novel insights into a poorly understood component of intercommunication between the brain and the immune system by showing that psychological stress can modify lymphocytes in a manner that may boost resilience to psychological stress. To demonstrate the influence of the adaptive immune system on mood states, we previously showed that cells from lymph nodes of socially defeated mice, but not from unstressed mice, conferred anxiolytic and antidepressant-like effects and elevated hippocampal cell proliferation when transferred into naïve lymphopenic Rag2(-/-) mice. In the present study, we asked whether similar transfer could be anxiolytic and antidepressant when done in animals that had been rendered anxious and depressed by chronic psychological stress. First, we demonstrated that lymphopenic Rag2(-/-) mice and their wild-type C57BL/6 mouse counterparts had similar levels of affect normally. Second, we found that following chronic (14days) restraint stress, both groups displayed an anxious and depressive-like phenotype and decreased hippocampal cell proliferation. Third, we showed that behavior in the open field test and light/dark box was normalized in the restraint-stressed Rag2(-/-) mice following adoptive transfer of lymph node cells from green fluorescent protein (GFP) expressing donor mice previously exposed to chronic (14days) of social defeat stress. Cells transferred from unstressed donor mice had no effect on behavior. Immunolabeling of GFP+ cells confirmed that tissue engraftment had occurred at 14days after transfer. We found GFP+ lymphocytes in the spleen, lymph nodes, blood, choroid plexus, and meninges of the recipient Rag2(-/-) mice. The findings suggest that the adaptive immune system may play a key role in promoting recovery from chronic stress. The data support using lymphocytes as a novel therapeutic target for anxiety states. PMID:27109071

  20. Our Immune System

    MedlinePlus

    Our Immune System A story for children with primary immunodeficiency diseases Written by Sara LeBien IMMUNE DEFICIENCY FOUNDATION A note ... who are immune deficient to better understand their immune system. What is a “ B-cell, ” a “ T-cell, ” ...

  1. Immunization for Women

    MedlinePlus

    ... nfid.org/#sthash.eZ72dCSP.dpuf Diseases & Vaccines Overview Immunization Schedules Talk to you doctor about your immunization ... years Immunization Schedule for Children, 7-18 years Immunization News July 8, 2016 HPV-related cancers on ...

  2. Your Child's Immunizations

    MedlinePlus

    ... Things to Know About Zika & Pregnancy Your Child's Immunizations KidsHealth > For Parents > Your Child's Immunizations Print A A A Text Size What's in ... But in both cases, the protection is temporary. Immunization (vaccination) is a way of creating immunity to ...

  3. Immune modulatory function of abundant immune-related microRNAs in microvesicles from bovine colostrum.

    PubMed

    Sun, Qi; Chen, Xi; Yu, Jianxiong; Zen, Ke; Zhang, Chen-Yu; Li, Liang

    2013-03-01

    Colostrum provides essential nutrients and immunologically active factors that are beneficial to newborns. Our previous work demonstrated that milk contains large amounts of miRNA that is largely stored in milk-derived microvesicles (MVs). In the present study, we found that the MVs from colostrum contain significantly higher levels of several immune-related miRNAs. We hypothesized that the colostrum MVs may transfer the immune-related miRNAs into cells, which contribute to its immune modulatory feature. We isolated colostrum MVs by ultracentrifugation and demonstrated several immune modulation features associated with miRNAs. We also provide evidence that the physical structure of milk-derived MVs is essential for transfer miRNAs and following immune modulation effect. Moreover, we found that colostrum powder-derived MVs also contains higher levels of immune-related miRNAs that display similar immune modulation effects. Taken together, these results show that MV-containing immunerelated miRNAs may be a novel mechanism by which colostrum modulates body immune response. PMID:23483481

  4. Understanding Herd Immunity.

    PubMed

    Metcalf, C J E; Ferrari, M; Graham, A L; Grenfell, B T

    2015-12-01

    Individual immunity is a powerful force affecting host health and pathogen evolution. Importantly, the effects of individual immunity also scale up to affect pathogen transmission dynamics and the success of vaccination campaigns for entire host populations. Population-scale immunity is often termed 'herd immunity'. Here we outline how individual immunity maps to population outcomes and discuss implications for control of infectious diseases. Particular immunological characteristics may be more or less likely to result in a population level signature of herd immunity; we detail this and also discuss other population-level outcomes that might emerge from individual-level immunity.

  5. Integrated Immune Experiment

    NASA Technical Reports Server (NTRS)

    Crucian, Brian

    2009-01-01

    This viewgraph presentation reviews NASA's Integrated Immune Experiment. The objectives include: 1) Address significant lack of data regarding immune status during flight; 2) Replace several recent immune studies with one comprehensive study that will include in-flight sampling; 3) Determine the in-flight status of immunity, physiological stress, viral immunity/reactivation; 4) Determine the clinical risk related to immune dysregulation for exploration class spaceflight; and 5) Determine the appropriate monitoring strategy for spaceflight-associated immune dysfunction, that could be used for the evaluation of countermeasures.

  6. Induction/Engineering, Detection, Selection, and Expansion of Clinical-Grade Human Antigen-Specific CD8+ Cytotoxic T Cell Clones for Adoptive Immunotherapy

    PubMed Central

    Jeras, Matjaž; Bricl, Irena; Zorec, Robert; Švajger, Urban

    2010-01-01

    Adoptive transfer of effector antigen-specific immune cells is becoming a promising treatment option in allogeneic transplantation, infectious diseases, cancer, and autoimmune disorders. Within this context, the important role of CD8+ cytotoxic T cells (CTLs) is objective of intensive studies directed to their in vivo and ex vivo induction, detection, selection, expansion, and therapeutic effectiveness. Additional questions that are being addressed by the scientific community are related to the establishment and maintenance of their longevity and memory state as well as to defining critical conditions underlying their transitions between discrete, but functionally different subtypes. In this article we review and comment latest approaches and techniques used for preparing large amounts of antigen-specific CTLs, suitable for clinical use. PMID:20224660

  7. Update on international adoption: focus on Russia.

    PubMed

    McGuinness, Teena M; Robinson, Cheryl Broadus

    2011-06-01

    American families will continue to adopt children from foreign countries; the desire to have a child transcends national boundaries. Sadly, not all adoptions have happy outcomes. A recent and well-reported incident involved an American mother, who, exasperated with her adopted son's severe behavioral problems, returned him to Russia, alone, on an aircraft. Other tragic reports involve internationally adopted children who have died at the hands of their American parents. This article provides an overview of the consequences of institutionalization as a risk factor for behavioral health of children; implications for nursing care of adoptive families follow. PMID:21598869

  8. Immune Suppression and Immune Activation in Depression

    PubMed Central

    Blume, Joshua; Douglas, Steven D.; Evans, Dwight L.

    2010-01-01

    Depression has been characterized as a disorder of both immune suppression and immune activation. Markers of impaired cellular immunity (decreased natural killer cell cytotoxicity) and inflammation (elevated IL-6, TNFα, CRP) have been associated with depression. These immunological markers have been associated with other medical illnesses, suggesting that immune dysregulation may be a central feature common to both depression and to its frequent medical comorbidities. Yet the significant associations of findings of both immune suppression and immune activation with depression raise questions concerning the relationship between these two classes of immunological observations. Depressed populations are heterogeneous groups, and there may be differences in the immune profiles of populations that are more narrowly defined in terms of symptom profile and/or demographic features. There have been few reports concurrently investigating markers of immune suppression and immune activation in the same depressed individuals. An emerging preclinical literature suggests that chronic inflammation may directly contribute to the pathophysiology of immune suppression in the context of illnesses such as cancer and rheumatoid arthritis. This literature provides us with specific immunoregulatory mechanisms mediating these relationships that could also explain differences in immune disturbances between subsets of depressed individuals We propose a research agenda emphasizing the assessment of these immunoregulatory mechanisms in large samples of depressed subjects as a means to define the relationships among immune findings (suppression and/or activation) within the same depressed individuals and to characterize subsets of depressed subjects based on shared immune profiles. Such a program of research, building on and integrating our knowledge of the psychoneuroimmunology of depression, could lead to innovation in the assessment and treatment of depression and its medical comorbidities

  9. Adoptive immunotherapy of advanced melanoma.

    PubMed

    Shapira-Frommer, Ronnie; Schachter, Jacob

    2012-09-01

    Adoptive cell therapy (ACT) has emerged as an effective therapy for patients with metastatic melanoma. Since the first introduction of the protocol in 1988 [1], major improvements have been achieved with response rates of 40%-72% among patients who were resistant to previous treatment lines. Both cell product and conditioning regimen are major determinants of treatment efficacy; therefore, developing ACT protocols explore diverse ways to establish autologous intra-tumoral lymphocyte cultures or peripheral effector cells as well as different lymphodepleting regimens. While a proof of feasibility and a proof of concept had been established with previous published results, ACT will need to move beyond single-center experiences, to confirmatory, multi-center studies. If ACT is to move into widespread practice, it will be necessary to develop reproducible high quality cell production methods and accepted lymphodepleting regimen. Two new drugs, ipilimumab (Yervoy, Bristol-Myers Squibb) and vemurafenib (Zelboraf, Roche), were approved in 2011 for the treatment of metastatic melanoma based on positive phase III trials. Both drugs show a clear overall survival benefit, so the timing of when to use ACT will need to be carefully thought out. In contrast to these 2 new, commercially available outpatient treatments, ACT is a personally-specified product and labor-intensive therapy that demands both acquisition of high standard laboratory procedures and close clinical inpatient monitoring during treatment. It is unique among other anti-melanoma treatments, providing the potential for a durable response following a single, self-limited treatment. This perspective drives the efforts to make this protocol accessible for more patients and to explore modifications that may optimize treatment results.

  10. [Attachment and Adoption: Diagnostics, Psychopathology, and Therapy].

    PubMed

    Brisch, Karl-Heinz

    2015-01-01

    This presentation describes the development of attachment between adopted children and their adoptive parents with a focus on the particular issues seen in international adoptions. The questions of settling in, trauma in the country of origin, and the motivations of the adoptive parents will be discussed. Diagnosis and various psychopathological manifestations will be examined, as will outpatient and inpatient modes of therapy. The treatment of children of various ages will be covered along with the necessity for intensive counseling and psychotherapy for the adoptive parents. This will enable the parents to work through early trauma, which will give them and their adopted child the basis for developing healthy attachment patterns. This in turn will enable the child to mature and integrate into society. Possibilities of prevention are discussed. Many of the approaches discussed here regarding attachment and adoption may be applied to foster children and their foster parents. PMID:26645775

  11. [Attachment and Adoption: Diagnostics, Psychopathology, and Therapy].

    PubMed

    Brisch, Karl-Heinz

    2015-01-01

    This presentation describes the development of attachment between adopted children and their adoptive parents with a focus on the particular issues seen in international adoptions. The questions of settling in, trauma in the country of origin, and the motivations of the adoptive parents will be discussed. Diagnosis and various psychopathological manifestations will be examined, as will outpatient and inpatient modes of therapy. The treatment of children of various ages will be covered along with the necessity for intensive counseling and psychotherapy for the adoptive parents. This will enable the parents to work through early trauma, which will give them and their adopted child the basis for developing healthy attachment patterns. This in turn will enable the child to mature and integrate into society. Possibilities of prevention are discussed. Many of the approaches discussed here regarding attachment and adoption may be applied to foster children and their foster parents.

  12. Transituational Immunization and Therapy of Learned Helplessness in the Rat

    ERIC Educational Resources Information Center

    Maier, Steven F.; Williams, Jon L.

    1977-01-01

    These experiments are addressed specifically to the question of whether transituational transfer of immunizing and therapeutic effects will occur when these procedures involve responses and settings which are very different from those used in final testing. (Author/RK)

  13. Role of CD4(+) and CD8α(+) T cells in protective immunity against Edwardsiella tarda infection of ginbuna crucian carp, Carassius auratus langsdorfii.

    PubMed

    Yamasaki, Masatoshi; Araki, Kyosuke; Nakanishi, Teruyuki; Nakayasu, Chihaya; Yamamoto, Atsushi

    2014-01-01

    Edwardsiella tarda is an intracellular pathogen that causes edwardsiellosis in fish. Our previous study suggests that cell-mediated immunity (CMI) plays an essential role in protection against E. tarda infection. In the present study, we adoptively transferred T-cell subsets sensitized with E. tarda to isogenic naïve ginbuna crucian carp to determination the T-cell subsets involved in protecting fish from E. tarda infection. Recipients of CD4(+) and CD8α(+) cells acquired significant resistance to infection with E. tarda 8 days after sensitization, indicating that helper T cells and cytotoxic T lymphocytes plays crucial roles in protective immunity to E. tarda. Moreover, transfer of sensitized CD8α(+) cells up-regulated the expression of genes encoding interferon-γ (IFN-γ) and perforin, suggesting that protective immunity to E. tarda involves cell-mediated cytotoxicity and interferon-γ-mediated induction of CMI. The results establish that CMI plays a crucial role in immunity against E. tarda. These findings provide novel insights into understanding the role of CMI to intracellular pathogens of fish.

  14. Differential effects of myelin basic protein-activated Th1 and Th2 cells on the local immune microenvironment of injured spinal cord.

    PubMed

    Hu, Jian-Guo; Shi, Ling-Ling; Chen, Yue-Juan; Xie, Xiu-Mei; Zhang, Nan; Zhu, An-You; Jiang, Zheng-Song; Feng, Yi-Fan; Zhang, Chen; Xi, Jin; Lü, He-Zuo

    2016-03-01

    Myelin basic protein (MBP) activated T cells (MBP-T) play an important role in the damage and repair process of the central nervous system (CNS). However, whether these cells play a beneficial or detrimental role is still a matter of debate. Although some studies showed that MBP-T cells are mainly helper T (Th) cells, their subtypes are still not very clear. One possible explanation for MBP-T immunization leading to conflicting results may be the different subtypes of T cells are responsible for distinct effects. In this study, the Th1 and Th2 type MBP-T cells (MBP-Th1 and -Th2) were polarized in vitro, and their effects on the local immune microenvironment and tissue repair of spinal cord injury (SCI) after adoptive immunization were investigated. In MBP-Th1 cell transferred rats, the high levels of pro-inflammatory cells (Th1 cells and M1 macrophages) and cytokines (IFN-γ, TNF-α, -β, IL-1β) were detected in the injured spinal cord; however, the anti-inflammatory cells (Th2 cells, regulatory T cells, and M2 macrophages) and cytokines (IL-4, -10, and -13) were found in MBP-Th2 cell transferred animals. MBP-Th2 cell transfer resulted in decreased lesion volume, increased myelination of axons, and preservation of neurons. This was accompanied by significant locomotor improvement. These results indicate that MBP-Th2 adoptive transfer has beneficial effects on the injured spinal cord, in which the increased number of Th2 cells may alter the local microenvironment from one primarily populated by Th1 and M1 cells to another dominated by Th2, Treg, and M2 cells and is conducive for SCI repair.

  15. A Phase I Study on Adoptive Immunotherapy Using Gene-Modified T Cells for Ovarian Cancer

    PubMed Central

    Kershaw, Michael H.; Westwood, Jennifer A.; Parker, Linda L.; Wang, Gang; Eshhar, Zelig; Mavroukakis, Sharon A.; White, Donald E.; Wunderlich, John R.; Canevari, Silvana; Rogers-Freezer, Linda; Chen, Clara C.; Yang, James C.; Rosenberg, Steven A.; Hwu, Patrick

    2007-01-01

    Purpose A phase I study was conducted to assess the safety of adoptive immunotherapy using gene-modified autologous T cells for the treatment of metastatic ovarian cancer. Experimental Design T cells with reactivity against the ovarian cancer – associated antigen α-folate receptor (FR) were generated by genetic modification of autologous T cells with a chimeric gene incorporating an anti-FR single-chain antibody linked to the signaling domain of the Fc receptor γ chain. Patients were assigned to one of two cohorts in the study. Eight patients in cohort 1received a dose escalation of T cells in combination with high-dose interleukin-2, and six patients in cohort 2 received dual-specific T cells (reactive with both FR and allogeneic cells) followed by immunization with allogeneic peripheral blood mononuclear cells. Results Five patients in cohort 1 experienced some grade 3 to 4 treatment-related toxicity that was probably due to interleukin-2 administration, which could be managed using standard measures. Patients in cohort 2 experienced relatively mild side effects with grade 1to 2 symptoms. No reduction in tumor burden was seen in any patient. Tracking 111In-labeled adoptively transferred T cells in cohort 1revealed a lack of specific localization of T cells to tumor except in one patient where some signal was detected in a peritoneal deposit. PCR analysis showed that gene-modified T cells were present in the circulation in large numbers for the first 2 days after transfer, but these quickly declined to be barely detectable 1month later in most patients. An inhibitory factor developed in the serum of three of six patients tested over the period of treatment, which significantly reduced the ability of gene-modified T cells to respond against FR+ tumor cells. Conclusions Large numbers of gene-modified tumor-reactive T cells can be safely given to patients, but these cells do not persist in large numbers long term. Future studies need to employ strategies to

  16. 43 CFR 4750.4-2 - Adoption fee.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... wild horses and burros? You must pay an adoption fee for each wild horse or burro you adopt. Usually... adoption events for wild horses or burros. At competitive adoptions, qualified adopters set adoption fees... Director may reduce or waive the fee when wild horses or burros are un-adoptable at the base adoption...

  17. 43 CFR 4750.4-2 - Adoption fee.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... wild horses and burros? You must pay an adoption fee for each wild horse or burro you adopt. Usually... adoption events for wild horses or burros. At competitive adoptions, qualified adopters set adoption fees... Director may reduce or waive the fee when wild horses or burros are un-adoptable at the base adoption...

  18. 43 CFR 4750.4-2 - Adoption fee.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... wild horses and burros? You must pay an adoption fee for each wild horse or burro you adopt. Usually... adoption events for wild horses or burros. At competitive adoptions, qualified adopters set adoption fees... Director may reduce or waive the fee when wild horses or burros are un-adoptable at the base adoption...

  19. 43 CFR 4750.4-2 - Adoption fee.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... wild horses and burros? You must pay an adoption fee for each wild horse or burro you adopt. Usually... adoption events for wild horses or burros. At competitive adoptions, qualified adopters set adoption fees... Director may reduce or waive the fee when wild horses or burros are un-adoptable at the base adoption...

  20. Heme oxygenase and the immune system in normal and pathological pregnancies

    PubMed Central

    Ozen, Maide; Zhao, Hui; Lewis, David B.; Wong, Ronald J.; Stevenson, David K.

    2015-01-01

    Normal pregnancy is an immunotolerant state. Many factors, including environmental, socioeconomic, genetic, and immunologic changes by infection and/or other causes of inflammation, may contribute to inter-individual differences resulting in a normal or pathologic pregnancy. In particular, imbalances in the immune system can cause many pregnancy-related diseases, such as infertility, abortions, pre-eclampsia, and preterm labor, which result in maternal/fetal death, prematurity, or small-for-gestational age newborns. New findings imply that myeloid regulatory cells and regulatory T cells (Tregs) may mediate immunotolerance during normal pregnancy. Effector T cells (Teffs) have, in contrast, been implicated to cause adverse pregnancy outcomes. Furthermore, feto-maternal tolerance affects the developing fetus. It has been shown that the Treg/Teff balance affects litter size and adoptive transfer of pregnancy-induced Tregs can prevent fetal rejection in the mouse. Heme oxygenase-1 (HO-1) has a protective role in many conditions through its anti-inflammatory, anti-apoptotic, antioxidative, and anti-proliferative actions. HO-1 is highly expressed in the placenta and plays a role in angiogenesis and placental vascular development and in regulating vascular tone in pregnancy. In addition, HO-1 is a major regulator of immune homeostasis by mediating crosstalk between innate and adaptive immune systems. Moreover, HO-1 can inhibit inflammation-induced phenotypic maturation of immune effector cells and pro-inflammatory cytokine secretion and promote anti-inflammatory cytokine production. HO-1 may also be associated with T-cell activation and can limit immune-based tissue injury by promoting Treg suppression of effector responses. Thus, HO-1 and its byproducts may protect against pregnancy complications by its immunomodulatory effects, and the regulation of HO-1 or its downstream effects has the potential to prevent or treat pregnancy complications and prematurity. PMID

  1. Heme oxygenase and the immune system in normal and pathological pregnancies.

    PubMed

    Ozen, Maide; Zhao, Hui; Lewis, David B; Wong, Ronald J; Stevenson, David K

    2015-01-01

    Normal pregnancy is an immunotolerant state. Many factors, including environmental, socioeconomic, genetic, and immunologic changes by infection and/or other causes of inflammation, may contribute to inter-individual differences resulting in a normal or pathologic pregnancy. In particular, imbalances in the immune system can cause many pregnancy-related diseases, such as infertility, abortions, pre-eclampsia, and preterm labor, which result in maternal/fetal death, prematurity, or small-for-gestational age newborns. New findings imply that myeloid regulatory cells and regulatory T cells (Tregs) may mediate immunotolerance during normal pregnancy. Effector T cells (Teffs) have, in contrast, been implicated to cause adverse pregnancy outcomes. Furthermore, feto-maternal tolerance affects the developing fetus. It has been shown that the Treg/Teff balance affects litter size and adoptive transfer of pregnancy-induced Tregs can prevent fetal rejection in the mouse. Heme oxygenase-1 (HO-1) has a protective role in many conditions through its anti-inflammatory, anti-apoptotic, antioxidative, and anti-proliferative actions. HO-1 is highly expressed in the placenta and plays a role in angiogenesis and placental vascular development and in regulating vascular tone in pregnancy. In addition, HO-1 is a major regulator of immune homeostasis by mediating crosstalk between innate and adaptive immune systems. Moreover, HO-1 can inhibit inflammation-induced phenotypic maturation of immune effector cells and pro-inflammatory cytokine secretion and promote anti-inflammatory cytokine production. HO-1 may also be associated with T-cell activation and can limit immune-based tissue injury by promoting Treg suppression of effector responses. Thus, HO-1 and its byproducts may protect against pregnancy complications by its immunomodulatory effects, and the regulation of HO-1 or its downstream effects has the potential to prevent or treat pregnancy complications and prematurity. PMID

  2. Economic incentives and foster child adoption.

    PubMed

    Argys, Laura; Duncan, Brian

    2013-06-01

    Every year, a large number of children in the United States enter the foster care system. Many of them are eventually reunited with their biological parents or quickly adopted. A significant number, however, face long-term foster care, and some of these children are eventually adopted by their foster parents. The decision by foster parents to adopt their foster child carries significant economic consequences, including for feiting foster care payments while also assuming responsibility for medical, legal, and educational expenses, to name a few. Since 1980, U.S. states have begun to offer adoption subsidies to offset some of these expenses, significantly lowering the cost of adopting a child who is in the foster care system. This article presents empirical evidence of the role that these economic incentives play in foster parents' decision of when, or if, to adopt their foster child. We find that adoption subsidies increase adoptions through two distinct price mechanisms: by lowering the absolute cost of adoption, and by lowering the relative cost of adoption versus long-term foster care.

  3. Changes in Motivation for Adoption, Value Orientations and Behavior in Three Generations of Adoptive Parents.

    ERIC Educational Resources Information Center

    Hoksbergen, Rene A. C.

    1998-01-01

    Hypothesizes that in this century a pattern of three generations of adoptive parents has developed, differing in motives and attitudes toward adoption: traditional-closed, open-idealistic, and materialistic-realistic. Maintains that adoption has lost its taboo character, domestic adoption is decreasing or has almost vanished (Scandinavia,…

  4. Inflammatory bowel disease: an immunity-mediated condition triggered by bacterial infection with Helicobacter hepaticus.

    PubMed Central

    Cahill, R J; Foltz, C J; Fox, J G; Dangler, C A; Powrie, F; Schauer, D B

    1997-01-01

    Inflammatory bowel disease (IBD) is thought to result from either an abnormal immunological response to enteric flora or a normal immunological response to a specific pathogen. No study to date has combined both factors. The present studies were carried out with an immunologically manipulated mouse model of IBD. Mice homozygous for the severe combined immunodeficiency (scid) mutation develop IBD with adoptive transfer of CD4+ T cells expressing high levels of CD45RB (CD45RB(high) CD4+ T cells). These mice do not develop IBD in germfree conditions, implicating undefined intestinal flora in the pathogenesis of lesions. In controlled duplicate studies, the influence of a single murine pathogen, Helicobacter hepaticus, in combination with the abnormal immunological response on the development of IBD was assessed. The combination of H. hepaticus infection and CD45RB(high) CD4+ T-cell reconstitution resulted in severe disease expression similar to that observed in human IBD. This study demonstrates that IBD develops in mice as a consequence of an abnormal immune response in the presence of a single murine pathogen, H. hepaticus. The interaction of host immunity and a single pathogen in this murine system provides a novel model of human IBD, an immunity-mediated condition triggered by bacterial infection. PMID:9234764

  5. Helminth Regulation of Immunity: A Three-pronged Approach to Treat Colitis.

    PubMed

    Lopes, Fernando; Matisz, Chelsea; Reyes, José L; Jijon, Humberto; Al-Darmaki, Ahmed; Kaplan, Gilaad G; McKay, Derek M

    2016-10-01

    By reputation, the parasite is a pariah, an unwelcome guest. Infection with helminth parasites evokes stereotypic immune responses in humans and mice that are dominated by T helper (Th)-2 responses; thus, a hypothesis arises that infection with helminths would limit immunopathology in concomitant inflammatory disease. Although infection with some species of helminths can cause devastating disease and affect the course of microbial infections, analyses of rodent models of inflammatory disease reveal that infection with helminth parasites, or treatment with helminth extracts, can limit the severity of autoinflammatory disease, including colitis. Intriguing, but fewer, studies show that adoptive transfer of myeloid immune cells treated with helminth products/extracts in vitro can suppress inflammation. Herein, 3 facets of helminth therapy are reviewed and critiqued: treatment with viable ova or larvae, treatment with crude extracts of the worm or purified molecules, and cellular immunotherapy. The beneficial effect of helminth therapy often converges on the mobilization of IL-10 and regulatory/alternatively activated macrophages, while there are reports on transforming growth factor (TGF)-β, regulatory T cells and dendritic cells, and recent data suggest that helminth-evoked changes in the microbiota should be considered when defining anticolitic mechanisms. We speculate that if the data from animal models translate to humans, noting the heterogeneity therein, then the choice between use of viable helminth ova, helminth extracts/molecules or antigen-pulsed immune cells could be matched to disease management in defined cohorts of patients with inflammatory bowel disease.

  6. Immunization with gastric H+/K(+)-ATPase induces a reversible autoimmune gastritis.

    PubMed

    Scarff, K J; Pettitt, J M; Van Driel, I R; Gleeson, P A; Toh, B H

    1997-09-01

    The gastric H+/K(+)-ATPase has been implicated as a major autoantigen in pernicious anaemia in humans and in thymectomy-induced autoimmune gastritis in mice. Here we have shown that autoimmune gastritis can be generated by direct immunization of non-thymectomized BALB/c mice with mouse gastric H+/K(+)-ATPase in complete Freund's adjuvant. The gastritis was characterized by infiltration of the gastric submucosa and mucosa with macrophages, CD4+ and CD8+ T cells, and B cells and by circulating autoantibodies to the H+/K(+)-ATPase. The mononuclear infiltrate within the gastric mucosa was accompanied by loss of parietal and zymogenic cells and accumulation of small immature epithelial cells. Splenocytes from gastritic mice adoptively transferred gastritis to naive recipients. Cessation of immunization resulted in decrease in autoantibody titre and regeneration of parietal and zymogenic cells. The results directly confirm that the gastric H+/K(+)-ATPase is the causative autoantigen in the genesis of autoimmune gastritis. Recovery of the lesion following cessation of immunization suggests that homeostatic mechanisms can reverse a destructive autoimmune process.

  7. Helminth Regulation of Immunity: A Three-pronged Approach to Treat Colitis.

    PubMed

    Lopes, Fernando; Matisz, Chelsea; Reyes, José L; Jijon, Humberto; Al-Darmaki, Ahmed; Kaplan, Gilaad G; McKay, Derek M

    2016-10-01

    By reputation, the parasite is a pariah, an unwelcome guest. Infection with helminth parasites evokes stereotypic immune responses in humans and mice that are dominated by T helper (Th)-2 responses; thus, a hypothesis arises that infection with helminths would limit immunopathology in concomitant inflammatory disease. Although infection with some species of helminths can cause devastating disease and affect the course of microbial infections, analyses of rodent models of inflammatory disease reveal that infection with helminth parasites, or treatment with helminth extracts, can limit the severity of autoinflammatory disease, including colitis. Intriguing, but fewer, studies show that adoptive transfer of myeloid immune cells treated with helminth products/extracts in vitro can suppress inflammation. Herein, 3 facets of helminth therapy are reviewed and critiqued: treatment with viable ova or larvae, treatment with crude extracts of the worm or purified molecules, and cellular immunotherapy. The beneficial effect of helminth therapy often converges on the mobilization of IL-10 and regulatory/alternatively activated macrophages, while there are reports on transforming growth factor (TGF)-β, regulatory T cells and dendritic cells, and recent data suggest that helminth-evoked changes in the microbiota should be considered when defining anticolitic mechanisms. We speculate that if the data from animal models translate to humans, noting the heterogeneity therein, then the choice between use of viable helminth ova, helminth extracts/molecules or antigen-pulsed immune cells could be matched to disease management in defined cohorts of patients with inflammatory bowel disease. PMID:27575495

  8. Dynamic Immune Cell Recruitment After Murine Pulmonary Aspergillus fumigatus Infection under Different Immunosuppressive Regimens

    PubMed Central

    Kalleda, Natarajaswamy; Amich, Jorge; Arslan, Berkan; Poreddy, Spoorthi; Mattenheimer, Katharina; Mokhtari, Zeinab; Einsele, Hermann; Brock, Matthias; Heinze, Katrin Gertrud; Beilhack, Andreas

    2016-01-01

    Humans are continuously exposed to airborne spores of the saprophytic fungus Aspergillus fumigatus. However, in healthy individuals pulmonary host defense mechanisms efficiently eliminate the fungus. In contrast, A. fumigatus causes devastating infections in immunocompromised patients. Host immune responses against A. fumigatus lung infections in immunocompromised conditions have remained largely elusive. Given the dynamic changes in immune cell subsets within tissues upon immunosuppressive therapy, we dissected the spatiotemporal pulmonary immune response after A. fumigatus infection to reveal basic immunological events that fail to effectively control invasive fungal disease. In different immunocompromised murine models, myeloid, notably neutrophils, and macrophages, but not lymphoid cells were strongly recruited to the lungs upon infection. Other myeloid cells, particularly dendritic cells and monocytes, were only recruited to lungs of corticosteroid treated mice, which developed a strong pulmonary inflammation after infection. Lymphoid cells, particularly CD4+ or CD8+ T-cells and NK cells were highly reduced upon immunosuppression and not recruited after A. fumigatus infection. Moreover, adoptive CD11b+ myeloid cell transfer rescued cyclophosphamide immunosuppressed mice from lethal A. fumigatus infection but not cortisone and cyclophosphamide immunosuppressed mice. Our findings illustrate that CD11b+ myeloid cells are critical for anti-A. fumigatus defense under cyclophosphamide immunosuppressed conditions. PMID:27468286

  9. Depletion of CD4 T cells enhances immunotherapy for neuroblastoma after syngeneic HSCT but compromises development of antitumor immune memory.

    PubMed

    Jing, Weiqing; Gershan, Jill A; Johnson, Bryon D

    2009-04-30

    High-risk neuroblastoma remains a clinically challenging disease. Here, we report that a multifaceted immunotherapeutic approach including syngeneic hematopoietic stem cell transplantation (HSCT), adoptive transfer of sensitized T cells (from syngeneic donors vaccinated to tumor antigens), and early posttransplantation tumor vaccination can effectively treat mice with established neuroblastoma. Vaccination was an important component of this immunotherapy, as it resulted in enhanced and prolonged tumor-specific CD8 T-cell activity and improved antitumor efficacy. Surprisingly, CD4 cell depletion of mice given sensitized T cells resulted in better tumor-free survival, which was associated with an early increased expansion of CD8 T cells with an effector phenotype, increased numbers of tumor-reactive CD8 T cells, and increased tumor infiltration by CD8 T cells. However, in the absence of CD4 T cells, development of long-term tumor immunity (memory) was severely compromised as reflected by diminished CD8 T-cell recall responses and an inability to resist tumor rechallenge in vivo. Based on these results, a major challenge with this immunotherapeutic approach is how to obtain the ideal initial antitumor response but still preserve antitumor immune memory. These data suggest that identification and selective depletion of immune inhibitory CD4 T cells may be a strategy to enhance early antitumor immunity and induce a long-lasting tumor response after HSCT.

  10. Splenectomy inhibits non-small cell lung cancer growth by modulating anti-tumor adaptive and innate immune response

    PubMed Central

    Levy, Liran; Mishalian, Inbal; Bayuch, Rachel; Zolotarov, Lida; Michaeli, Janna; Fridlender, Zvi G

    2015-01-01

    It has been shown that inhibitors of the immune system reside in the spleen and inhibit the endogenous antitumor effects of the immune system. We hypothesized that splenectomy would inhibit the growth of relatively large non-small lung cancer (NSCLC) tumors by modulating the systemic inhibition of the immune system, and in particular Myeloid Derived Suppressor Cells (MDSC). The effect of splenectomy was evaluated in several murine lung cancer models. We found that splenectomy reduces tumor growth and the development of lung metastases, but only in advanced tumors. In immune-deficient NOD-SCID mice the effect of splenectomy on tumor growth and metastatic spread disappeared. Splenectomy significantly reduced the presence of MDSC, and especially monocytic-MDSC in the circulation and inside the tumor. Specific reduction of the CCR2+ subset of monocytic MDSC was demonstrated, and the importance of the CCL2-CCR2 axis was further shown by a marked reduction in CCL2 following splenectomy. These changes were followed by changes in the macrophages contents of the tumors to become more antitumorigenic, and by increased activation of CD8+ Cytotoxic T-cells (CTL). By MDSC depletion, and adoptive transfer of MDSCs, we demonstrated that the effect of splenectomy on tumor growth was substantially mediated by MDSC cells. We conclude that the spleen is an important contributor to tumor growth and metastases, and that splenectomy can blunt this effect by depletion of MDSC, changing the amount and characteristics of myeloid cells and enhancing activation of CTL. PMID:26137413

  11. Parallel processing in immune networks

    NASA Astrophysics Data System (ADS)

    Agliari, Elena; Barra, Adriano; Bartolucci, Silvia; Galluzzi, Andrea; Guerra, Francesco; Moauro, Francesco

    2013-04-01

    In this work, we adopt a statistical-mechanics approach to investigate basic, systemic features exhibited by adaptive immune systems. The lymphocyte network made by B cells and T cells is modeled by a bipartite spin glass, where, following biological prescriptions, links connecting B cells and T cells are sparse. Interestingly, the dilution performed on links is shown to make the system able to orchestrate parallel strategies to fight several pathogens at the same time; this multitasking capability constitutes a remarkable, key property of immune systems as multiple antigens are always present within the host. We also define the stochastic process ruling the temporal evolution of lymphocyte activity and show its relaxation toward an equilibrium measure allowing statistical-mechanics investigations. Analytical results are compared with Monte Carlo simulations and signal-to-noise outcomes showing overall excellent agreement. Finally, within our model, a rationale for the experimentally well-evidenced correlation between lymphocytosis and autoimmunity is achieved; this sheds further light on the systemic features exhibited by immune networks.

  12. Theoretical aspects of immunity.

    PubMed

    Deem, Michael W; Hejazi, Pooya

    2010-01-01

    The immune system recognizes a myriad of invading pathogens and their toxic products. It does so with a finite repertoire of antibodies and T cell receptors. We here describe theories that quantify the dynamics of the immune system. We describe how the immune system recognizes antigens by searching the large space of receptor molecules. We consider in some detail the theories that quantify the immune response to influenza and dengue fever. We review theoretical descriptions of the complementary evolution of pathogens that occurs in response to immune system pressure. Methods including bioinformatics, molecular simulation, random energy models, and quantum field theory contribute to a theoretical understanding of aspects of immunity.

  13. Foxp3+ T cells inhibit antitumor immune memory modulated by mTOR inhibition.

    PubMed

    Wang, Yanping; Sparwasser, Tim; Figlin, Robert; Kim, Hyung L

    2014-04-15

    Inhibition of mTOR signaling enhances antitumor memory lymphocytes. However, pharmacologic mTOR inhibition also enhances regulatory T-cell (Treg) activity. To counter this effect, Treg control was added to mTOR inhibition in preclinical models. Tregs were controlled with CD4-depleting antibodies because CD4 depletion has high translational potential and already has a well-established safety profile in patients. The antitumor activity of the combination therapy was CD8 dependent and controlled growth of syngeneic tumors even when an adoptive immunotherapy was not used. Lymphocytes resulting from the combination therapy could be transferred into naïve mice to inhibit aggressive growth of lung metastases. The combination therapy enhanced CD8 memory formation as determined by memory markers and functional studies of immune recall. Removal of FoxP3-expressing T lymphocytes was the mechanism underlying immunologic memory formation following CD4 depletion. This was confirmed using transgenic DEREG (depletion of regulatory T cells) mice to specifically remove Foxp3(+) T cells. It was further confirmed with reciprocal studies where stimulation of immunologic memory because of CD4 depletion was completely neutralized by adoptively transferring tumor-specific Foxp3(+) T cells. Also contributing to tumor control, Tregs that eventually recovered following CD4 depletion were less immunosuppressive. These results provide a rationale for further study of mTOR inhibition and CD4 depletion in patients.

  14. Building Adoption of Visual Analytics Software

    SciTech Connect

    Chinchor, Nancy; Cook, Kristin A.; Scholtz, Jean

    2012-01-05

    Adoption of technology is always difficult. Issues such as having the infrastructure necessary to support the technology, training for users, integrating the technology into current processes and tools, and having the time, managerial support, and necessary funds need to be addressed. In addition to these issues, the adoption of visual analytics tools presents specific challenges that need to be addressed. This paper discusses technology adoption challenges and approaches for visual analytics technologies.

  15. Measures for Predictors of Innovation Adoption

    PubMed Central

    Chor, Ka Ho Brian; Wisdom, Jennifer P.; Olin, Su-Chin Serene; Hoagwood, Kimberly E.; Horwitz, Sarah M.

    2014-01-01

    Building on a narrative synthesis of adoption theories by Wisdom et al. (2013), this review identifies 118 measures associated with the 27 adoption predictors in the synthesis. The distribution of measures is uneven across the predictors and predictors vary in modifiability. Multiple dimensions and definitions of predictors further complicate measurement efforts. For state policymakers and researchers, more effective and integrated measurement can advance the adoption of complex innovations such as evidence-based practices. PMID:24740175

  16. [Choosing the name in international adoption].

    PubMed

    van Effenterre, Aude; Harf, Aurélie; Skandrani, Sandra; Taïeb, Olivier; Moro, Marie Rose

    2014-01-01

    In the context of international adoption, the question is raised of the links which the adoptive parents may or may not maintain with the culture of the child's birth country. The name which the adoptive parents choose reflects this questioning. A study was carried out into this subject with parents and children in order to gain a better understanding of the feelings of belonging, filiation and affiliation in these situations.

  17. Evaluation of a novel dog adoption program in two US communities.

    PubMed

    Mohan-Gibbons, Heather; Weiss, Emily; Garrison, Laurie; Allison, Meg

    2014-01-01

    Millions of dogs enter animal welfare organizations every year and only a fraction of them are adopted. Despite the most recent American Pet Products Association (APPA) data that nearly half the US population owns a dog, only 20% acquired their dog from an animal welfare organization. Studies show that people consider adopting from an animal shelter more often than they actually do, which indicates a potential market increase if programs can make shelter dogs more visible to adopters. This research focused on a novel adoption program where shelter dogs were transferred into foster homes who were tasked with finding an adopter. Shelter dogs were placed in the path of potential adopters and bypassed the need for the adopter to go to the shelter. The results show that this novel program was effective in a variety of ways including getting dogs adopted. Although length of stay was significantly longer for dogs in the program, the dogs were in a home environment, not taking up kennel space in the shelter. The program also had a lower rate of returns than dogs adopted at the shelter. The foster program tapped adopters in different geographical segments of the community than the dogs adopted from the shelter. By bringing shelter dogs to where adopters spend their time (ex: restaurants, parks, hair salons), the program potentially captured a segment of the population who might have obtained their dog from other sources besides the shelter (such as breeders or pet stores). This novel approach can be an effective method for adoption, has many benefits for shelters, and can tap into a new adopter market by engaging their community in a new way.

  18. TRANSFER STUDY.

    ERIC Educational Resources Information Center

    GREIVE, DONALD E.

    THIS 1967 STUDY AT LORAIN COUNTY COMMUNITY COLLEGE (LCCC) WAS UNDERTAKEN TO DISCOVER (1) THE PERCENTAGE OF CREDIT HOURS IN A UNIVERSITY PARALLEL PROGRAM ACCEPTED BY TRANSFER INSTITUTIONS, (2) THE STUDENT'S GPA BEFORE AND AFTER TRANSFER, AND (3) HOW MANY COLLEGES ACCEPTED LCCC'S TRANSFERS. INSTITUTIONS TO WHICH LCCC STUDENTS HAD HAD THEIR…

  19. Imbalanced immune homeostasis in immune thrombocytopenia.

    PubMed

    Yazdanbakhsh, Karina

    2016-04-01

    Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder resulting from low platelet counts caused by inadequate production as well as increased destruction by autoimmune mechanisms. As with other autoimmune disorders, chronic ITP is characterized by perturbations of immune homeostasis with hyperactivated effector cells as well as defective regulatory arm of the adaptive immune system, which will be reviewed here. Interestingly, some ITP treatments are associated with restoring the regulatory imbalance, although it remains unclear whether the immune system is redirected to a state of tolerance once treatment is discontinued. Understanding the mechanisms that result in breakdown of immune homeostasis in ITP will help to identify novel pathways for restoring tolerance and inhibiting effector cell responses. This information can then be translated into developing therapies for averting autoimmunity not only in ITP but also many autoimmune disorders. PMID:27312156

  20. Imbalanced immune homeostasis in immune thrombocytopenia.

    PubMed

    Yazdanbakhsh, Karina

    2016-04-01

    Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder resulting from low platelet counts caused by inadequate production as well as increased destruction by autoimmune mechanisms. As with other autoimmune disorders, chronic ITP is characterized by perturbations of immune homeostasis with hyperactivated effector cells as well as defective regulatory arm of the adaptive immune system, which will be reviewed here. Interestingly, some ITP treatments are associated with restoring the regulatory imbalance, although it remains unclear whether the immune system is redirected to a state of tolerance once treatment is discontinued. Understanding the mechanisms that result in breakdown of immune homeostasis in ITP will help to identify novel pathways for restoring tolerance and inhibiting effector cell responses. This information can then be translated into developing therapies for averting autoimmunity not only in ITP but also many autoimmune disorders.

  1. Exosomes and their roles in immune regulation and cancer.

    PubMed

    Greening, David W; Gopal, Shashi K; Xu, Rong; Simpson, Richard J; Chen, Weisan

    2015-04-01

    Exosomes, a subset of extracellular vesicles (EVs), function as a mode of intercellular communication and molecular transfer. Exosomes facilitate the direct extracellular transfer of proteins, lipids, and miRNA/mRNA/DNAs between cells in vitro and in vivo. The immunological activities of exosomes affect immunoregulation mechanisms including modulating antigen presentation, immune activation, immune suppression, immune surveillance, and intercellular communication. Besides immune cells, cancer cells secrete immunologically active exosomes that influence both physiological and pathological processes. The observation that exosomes isolated from immune cells such as dendritic cells (DCs) modulate the immune response has enforced the way these membranous vesicles are being considered as potential immunotherapeutic reagents. Indeed, tumour- and immune cell-derived exosomes have been shown to carry tumour antigens and promote immunity, leading to eradication of established tumours by CD8(+) T cells and CD4(+) T cells, as well as directly suppressing tumour growth and resistance to malignant tumour development. Further understanding of these areas of exosome biology, and especially of molecular mechanisms involved in immune cell targeting, interaction and manipulation, is likely to provide significant insights into immunorecognition and therapeutic intervention. Here, we review the emerging roles of exosomes in immune regulation and the therapeutic potential in cancer.

  2. Diversity of immune strategies explained by adaptation to pathogen statistics

    PubMed Central

    Mayer, Andreas; Mora, Thierry; Rivoire, Olivier; Walczak, Aleksandra M.

    2016-01-01

    Biological organisms have evolved a wide range of immune mechanisms to defend themselves against pathogens. Beyond molecular details, these mechanisms differ in how protection is acquired, processed, and passed on to subsequent generations—differences that may be essential to long-term survival. Here, we introduce a mathematical framework to compare the long-term adaptation of populations as a function of the pathogen dynamics that they experience and of the immune strategy that they adopt. We find that the two key determinants of an optimal immune strategy are the frequency and the characteristic timescale of the pathogens. Depending on these two parameters, our framework identifies distinct modes of immunity, including adaptive, innate, bet-hedging, and CRISPR-like immunities, which recapitulate the diversity of natural immune systems. PMID:27432970

  3. Syngeneic syrian hamster tumors feature tumor-infiltrating lymphocytes allowing adoptive cell therapy enhanced by oncolytic adenovirus in a replication permissive setting.

    PubMed

    Siurala, Mikko; Vähä-Koskela, Markus; Havunen, Riikka; Tähtinen, Siri; Bramante, Simona; Parviainen, Suvi; Mathis, J Michael; Kanerva, Anna; Hemminki, Akseli

    2016-05-01

    Adoptive transfer of tumor-infiltrating lymphocytes (TIL) has shown promising yet sometimes suboptimal results in clinical trials for advanced cancer, underscoring the need for approaches improving efficacy and safety. Six implantable syngeneic tumor cell lines of the Syrian hamster were used to initiate TIL cultures. TIL generated from tumor fragments cultured in human interleukin-2 (IL-2) for 10 d were adoptively transferred into tumor-bearing hamsters with concomitant intratumoral injections of oncolytic adenovirus (Ad5-D24) for the assessment of antitumor efficacy. Pancreatic cancer (HapT1) and melanoma (RPMI 1846) TIL exhibited potent and tumor-specific cytotoxicity in effector-to-target (E/T) assays. MHC Class I blocking abrogated the cell killing of RPMI 1846 TIL, indicating cytotoxic CD8(+) T-cell activity. When TIL were combined with Ad5-D24 in vitro, HapT1 tumor cell killing was significantly enhanced over single agents. In vivo, the intratumoral administration of HapT1 TIL and Ad5-D24 resulted in improved tumor growth control compared with either treatment alone. Additionally, splenocytes derived from animals treated with the combination of Ad5-D24 and TIL killed autologous tumor cells more efficiently than monotherapy-derived splenocytes, suggesting that systemic antitumor immunity was induced. For the first time, TIL of the Syrian hamster have been cultured, characterized and used therapeutically together with oncolytic adenovirus for enhancing the efficacy of TIL therapy. Our results support human translation of oncolytic adenovirus as an enabling technology for adoptive T-cell therapy of solid tumors.

  4. Syngeneic syrian hamster tumors feature tumor-infiltrating lymphocytes allowing adoptive cell therapy enhanced by oncolytic adenovirus in a replication permissive setting.

    PubMed

    Siurala, Mikko; Vähä-Koskela, Markus; Havunen, Riikka; Tähtinen, Siri; Bramante, Simona; Parviainen, Suvi; Mathis, J Michael; Kanerva, Anna; Hemminki, Akseli

    2016-05-01

    Adoptive transfer of tumor-infiltrating lymphocytes (TIL) has shown promising yet sometimes suboptimal results in clinical trials for advanced cancer, underscoring the need for approaches improving efficacy and safety. Six implantable syngeneic tumor cell lines of the Syrian hamster were used to initiate TIL cultures. TIL generated from tumor fragments cultured in human interleukin-2 (IL-2) for 10 d were adoptively transferred into tumor-bearing hamsters with concomitant intratumoral injections of oncolytic adenovirus (Ad5-D24) for the assessment of antitumor efficacy. Pancreatic cancer (HapT1) and melanoma (RPMI 1846) TIL exhibited potent and tumor-specific cytotoxicity in effector-to-target (E/T) assays. MHC Class I blocking abrogated the cell killing of RPMI 1846 TIL, indicating cytotoxic CD8(+) T-cell activity. When TIL were combined with Ad5-D24 in vitro, HapT1 tumor cell killing was significantly enhanced over single agents. In vivo, the intratumoral administration of HapT1 TIL and Ad5-D24 resulted in improved tumor growth control compared with either treatment alone. Additionally, splenocytes derived from animals treated with the combination of Ad5-D24 and TIL killed autologous tumor cells more efficiently than monotherapy-derived splenocytes, suggesting that systemic antitumor immunity was induced. For the first time, TIL of the Syrian hamster have been cultured, characterized and used therapeutically together with oncolytic adenovirus for enhancing the efficacy of TIL therapy. Our results support human translation of oncolytic adenovirus as an enabling technology for adoptive T-cell therapy of solid tumors. PMID:27467954

  5. Enhanced Immune Response in Immunodeficient Mice Improves Peripheral Nerve Regeneration Following Axotomy

    PubMed Central

    Bombeiro, André L.; Santini, Júlio C.; Thomé, Rodolfo; Ferreira, Elisângela R. L.; Nunes, Sérgio L. O.; Moreira, Bárbara M.; Bonet, Ivan J. M.; Sartori, Cesar R.; Verinaud, Liana; Oliveira, Alexandre L. R.

    2016-01-01

    Injuries to peripheral nerves cause loss of motor and sensory function, greatly affecting life quality. Successful repair of the lesioned nerve requires efficient cell debris removal, followed by axon regeneration and reinnervation of target organs. Such process is orchestrated by several cellular and molecular events in which glial and immune cells actively participate. It is known that tissue clearance is largely improved by macrophages, which activation is potentiated by cells and molecules of the acquired immune system, such as T helper lymphocytes and antibodies, respectively. In the present work, we evaluated the contribution of lymphocytes in the regenerative process of crushed sciatic nerves of immunocompetent (wild-type, WT) and T and B-deficient (RAG-KO) mice. In Knockout animals, we found increased amount of macrophages under basal conditions and during the initial phase of the regenerative process, that was evaluated at 2, 4, and 8 weeks after lesion (wal). That parallels with faster axonal regeneration evidenced by the quantification of neurofilament and a growth associated protein immunolabeling. The motor function, evaluated by the sciatic function index, was fully recovered in both mouse strains within 4 wal, either in a progressive fashion, as observed for RAG-KO mice, or presenting a subtle regression, as seen in WT mice between 2 and 3 wal. Interestingly, boosting the immune response by early adoptive transference of activated WT lymphocytes at 3 days after lesion improved motor recovery in WT and RAG-KO mice, which was not ameliorated when cells were transferred at 2 wal. When monitoring lymphocytes by in vivo imaging, in both mouse strains, cells migrated to the lesion site shortly after transference, remaining in the injured limb up to its complete motor recovery. Moreover, a first peak of hyperalgesia, determined by von-Frey test, was coincident with increased lymphocyte infiltration in the damaged paw. Overall, the present results suggest

  6. Immunity by equilibrium.

    PubMed

    Eberl, Gérard

    2016-08-01

    The classical model of immunity posits that the immune system reacts to pathogens and injury and restores homeostasis. Indeed, a century of research has uncovered the means and mechanisms by which the immune system recognizes danger and regulates its own activity. However, this classical model does not fully explain complex phenomena, such as tolerance, allergy, the increased prevalence of inflammatory pathologies in industrialized nations and immunity to multiple infections. In this Essay, I propose a model of immunity that is based on equilibrium, in which the healthy immune system is always active and in a state of dynamic equilibrium between antagonistic types of response. This equilibrium is regulated both by the internal milieu and by the microbial environment. As a result, alteration of the internal milieu or microbial environment leads to immune disequilibrium, which determines tolerance, protective immunity and inflammatory pathology.

  7. Immune Responses in Neonates

    PubMed Central

    Basha, Saleem; Surendran, Naveen; Pichichero, Michael

    2015-01-01

    Neonates have little immunological memory and a developing immune system, which increases their vulnerability to infectious agents. Recent advances in understanding of neonatal immunity indicate that both innate and adaptive responses are dependent on precursor frequency of lymphocytes, antigenic dose and mode of exposure. Studies in neonatal mouse models and human umbilical cord blood cells demonstrate the capability of neonatal immune cells to produce immune responses similar to adults in some aspects but not others. This review focuses mainly on the developmental and functional mechanisms of the human neonatal immune system. In particular, the mechanism of innate and adaptive immunity and the role of neutrophils, antigen presenting cells, differences in subclasses of T lymphocytes (Th1, Th2, Tregs) and B cells are discussed. In addition, we have included the recent developments in neonatal mouse immune system. Understanding neonatal immunity is essential to development of therapeutic vaccines to combat newly emerging infectious agents. PMID:25088080

  8. Immunity to cancer

    SciTech Connect

    Reif, A.E.; Mitchell, M.S.

    1985-01-01

    This book contains five sections, each containing several papers. The section titles are: Identification and Characterization of Tumor Antigens; Immune Responses to Tumor Antigens; Regulation of the Immune Response to Tumor Cells, Immunotherapy and Biomodulators, and Immunotherapy and Immunoprophylaxis.

  9. Immune System and Disorders

    MedlinePlus

    Your immune system is a complex network of cells, tissues, and organs that work together to defend against germs. It ... t, to find and destroy them. If your immune system cannot do its job, the results can be ...

  10. Technology transfer

    NASA Technical Reports Server (NTRS)

    Handley, Thomas

    1992-01-01

    The requirements for a successful technology transfer program and what such a program would look like are discussed. In particular, the issues associated with technology transfer in general, and within the Jet Propulsion Laboratory (JPL) environment specifically are addressed. The section on background sets the stage, identifies the barriers to successful technology transfer, and suggests actions to address the barriers either generally or specifically. The section on technology transfer presents a process with its supporting management plan that is required to ensure a smooth transfer process. Viewgraphs are also included.

  11. Envisaging the adoption process to strengthen gay- and lesbian-headed families: recommendations for adoption professionals.

    PubMed

    Matthews, John D; Cramer, Elizabeth P

    2006-01-01

    Although a growing number of child placement agencies are serving lesbians and gay men, a dearth of literature exists for adoption agency policies and practices related to working with this population. This article explores the unique characteristics and strengths of prospective gay and lesbian adoptive parents throughout each of the three phases of the adoption process-preplacement, placement, and postplacement-as well as provides suggestions for adoption professionals working with gays and lesbians. Data from a recent qualitative study of single, gay adoptive fathers are used to illustrate examples and expose areas of potential strengths of adoptive parents not generally explored in the preplacement or preparatory stage. Special attention also is given to the continuing needs of adoptive families headed by gays and lesbians after adoptive placement. Specifically explored are the needs for developing linkages with similar families, as well as providing resources designed to promote successful outcomes of adopted children raised by gays and lesbians.

  12. Predictors of race, adoption, and sexual orientation related socialization of adoptive parents of young children.

    PubMed

    Goldberg, Abbie E; Smith, JuliAnna Z

    2016-04-01

    Using a sample of 125 lesbian, gay, and heterosexual adoptive parent couples with young children (M = 6.32 years), this study examined predictors of direct socialization (preparation for adoptism, racism, and heterosexism) and indirect socialization (modeling interactions by responding to outsiders' inquiries about their child's adoptive status, racial background, or family structure). In terms of direct socialization, parents of older children tended to engage in more socialization around adoptism and heterosexism, and parents of daughters tended to engage in more socialization around racism and heterosexism. Greater perceived child interest in adoption was related to more direct socialization around adoptism. Parents of color reported more direct socialization around racism. Having a child of color was related to more direct socialization around heterosexism. Regarding indirect socialization, sexual minority parents reported more socialization around adoption and race. Greater perceived child interest in adoption was related to more indirect adoption socialization. Being more "out" was related to more indirect socialization around parent sexual orientation.

  13. Healthy depictions? Depicting adoption and adoption news events on broadcast news.

    PubMed

    Kline, Susan L; Chatterjee, Karishma; Karel, Amanda I

    2009-01-01

    Given that the public uses the media to learn about adoption as a family form, this study analyzes U.S. television news coverage of adoption between 2001 and 2005 (N = 309 stories), to identify the types of news events covered about adoption. A majority of news stories covered fraud, crime, legal disputes, and negative international adoption cases. Adoptees as defective or unhealthy were depicted more in negative news event stories, birth parents appeared less overall, and adoptive parents were most likely to have healthy depictions in positively oriented adoption experience, big family, and reunion stories. Although three quarters of the stories used primary adoption participants as news sources, one-third of the negative event stories did not contain healthy depictions of adoption participants. The authors discuss ways journalists and researchers might improve adoption news coverage.

  14. Synergistic innate and adaptive immune response to combination immunotherapy with anti-tumor antigen antibodies and extended serum half-life IL-2

    PubMed Central

    Zhu, Eric F.; Gai, Shuning A.; Opel, Cary F.; Kwan, Byron H.; Surana, Rishi; Mihm, Martin C.; Kauke, Monique J.; Moynihan, Kelly D.; Angelini, Alessandro; Williams, Robert T.; Stephan, Matthias T.; Kim, Jacob S.; Yaffe, Michael B.; Irvine, Darrell J.; Weiner, Louis M.; Dranoff, Glenn

    2015-01-01

    Summary Cancer immunotherapies under development have generally focused on either stimulating T-cell immunity or driving antibody-directed effector functions of the innate immune system such as antibody-dependent cell-mediated cytotoxicity (ADCC). We find that a combination of an anti-tumor antigen antibody and an untargeted IL-2 fusion protein with delayed systemic clearance induces significant tumor control in aggressive isogenic tumor models via a concerted innate and adaptive response involving neutrophils, NK cells, macrophages, and CD8+ T-cells. This combination therapy induces an intratumoral “cytokine storm” and extensive lymphocyte infiltration. Adoptive transfer of anti-tumor T-cells together with this combination therapy leads to robust cures of established tumors and establishment of immunological memory. PMID:25873172

  15. Synergistic innate and adaptive immune response to combination immunotherapy with anti-tumor antigen antibodies and extended serum half-life IL-2.

    PubMed

    Zhu, Eric F; Gai, Shuning A; Opel, Cary F; Kwan, Byron H; Surana, Rishi; Mihm, Martin C; Kauke, Monique J; Moynihan, Kelly D; Angelini, Alessandro; Williams, Robert T; Stephan, Matthias T; Kim, Jacob S; Yaffe, Michael B; Irvine, Darrell J; Weiner, Louis M; Dranoff, Glenn; Wittrup, K Dane

    2015-04-13

    Cancer immunotherapies under development have generally focused on either stimulating T cell immunity or driving antibody-directed effector functions of the innate immune system such as antibody-dependent cell-mediated cytotoxicity (ADCC). We find that a combination of an anti-tumor antigen antibody and an untargeted IL-2 fusion protein with delayed systemic clearance induces significant tumor control in aggressive isogenic tumor models via a concerted innate and adaptive response involving neutrophils, NK cells, macrophages, and CD8(+) T cells. This combination therapy induces an intratumoral "cytokine storm" and extensive lymphocyte infiltration. Adoptive transfer of anti-tumor T cells together with this combination therapy leads to robust cures of established tumors and development of immunological memory.

  16. Synergistic innate and adaptive immune response to combination immunotherapy with anti-tumor antigen antibodies and extended serum half-life IL-2.

    PubMed

    Zhu, Eric F; Gai, Shuning A; Opel, Cary F; Kwan, Byron H; Surana, Rishi; Mihm, Martin C; Kauke, Monique J; Moynihan, Kelly D; Angelini, Alessandro; Williams, Robert T; Stephan, Matthias T; Kim, Jacob S; Yaffe, Michael B; Irvine, Darrell J; Weiner, Louis M; Dranoff, Glenn; Wittrup, K Dane

    2015-04-13

    Cancer immunotherapies under development have generally focused on either stimulating T cell immunity or driving antibody-directed effector functions of the innate immune system such as antibody-dependent cell-mediated cytotoxicity (ADCC). We find that a combination of an anti-tumor antigen antibody and an untargeted IL-2 fusion protein with delayed systemic clearance induces significant tumor control in aggressive isogenic tumor models via a concerted innate and adaptive response involving neutrophils, NK cells, macrophages, and CD8(+) T cells. This combination therapy induces an intratumoral "cytokine storm" and extensive lymphocyte infiltration. Adoptive transfer of anti-tumor T cells together with this combination therapy leads to robust cures of established tumors and development of immunological memory. PMID:25873172

  17. Immune System Quiz

    MedlinePlus

    ... Homework? Here's Help White House Lunch Recipes Quiz: Immune System KidsHealth > For Kids > Quiz: Immune System Print A A A Text Size How much do you know about your immune system? Find out by taking this quiz! View Survey ...

  18. Aging changes in immunity

    MedlinePlus

    ... keeps your immune system strong. DO NOT smoke. Smoking weakens your immune system. Limit your intake of alcohol . Ask your provider how much alcohol is safe for you. Look into safety measures to prevent falls and injuries. A weak immune system can ...

  19. Immune Disorder HSCT Protocol

    ClinicalTrials.gov

    2016-01-09

    Immune Deficiency Disorders:; Severe Combined Immunodeficiency; Chronic Granulomatous Disease; X-linked Agammaglobulinemia; Wiskott-Aldrich Syndrome; Hyper-IgM; DiGeorge Syndrome; Chediak-Higashi Syndrome; Common Variable Immune Deficiency; Immune Dysregulatory Disorder:; Hemophagocytic Lymphohistiocytosis; IPEX; Autoimmune Lymphoproliferative Syndrome; X-linked Lymphoproliferative Syndrome

  20. The Immune System Game

    ERIC Educational Resources Information Center

    Work, Kirsten A.; Gibbs, Melissa A.; Friedman, Erich J.

    2015-01-01

    We describe a card game that helps introductory biology students understand the basics of the immune response to pathogens. Students simulate the steps of the immune response with cards that represent the pathogens and the cells and molecules mobilized by the immune system. In the process, they learn the similarities and differences between the…

  1. 75 FR 68166 - National Adoption Month, 2010

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-04

    ... From the Federal Register Online via the Government Publishing Office TD04NO10.016 [FR Doc. 2010... the United States of America the two hundred and thirty-fifth. (Presidential Sig.) [FR Doc. 2010-28117... small. National Adoption Day is a day of hope and happiness when courthouses finalize the adoptions...

  2. Predicting Language Outcomes for Internationally Adopted Children

    ERIC Educational Resources Information Center

    Glennen, Sharon L.

    2007-01-01

    Purpose: Language and speech are difficult to assess in newly arrived internationally adopted children. The purpose of this study was to determine if assessments completed when toddlers were first adopted could predict language outcomes at age 2. Local norms were used to develop early intervention guidelines that were evaluated against age 2…

  3. Covering Adoption: General Depictions in Broadcast News

    ERIC Educational Resources Information Center

    Kline, Susan L.; Karel, Amanda I.; Chatterjee, Karishma

    2006-01-01

    Using theories of stigma (Goffman, 1963) and media frames (Iyengar, 1991), 292 news stories pertaining to adoption that appeared on major broadcast networks between 2001 and 2004 were analyzed. Media coverage of adoptees contained more problematic than positive depictions. Although birth parents were not always depicted, adoptive parent and…

  4. Issues in Adoption and Foster Care.

    ERIC Educational Resources Information Center

    Hepworth, H. Philip

    This speech presents an overview of issues and trends in the provision of foster care and adoption services in Canada. The number of children "in care" in Canada (in foster homes, institutions, or adoptive homes) appears to have peaked around 1969 and declined thereafter. Information on contraceptives and the availaibility of abortions are seen as…

  5. Why Wasn't This Child Adopted?

    ERIC Educational Resources Information Center

    Raspberry, William

    1982-01-01

    Critizes the public child care policy with regard to adoption services through the story of "Joey", a black child in his teens. Shortly after his birth, Joey was sent by his teenage mother to a city agency for adoption and until now no real effort has been made to place him in a permanent home. (Author/MP)

  6. 43 CFR 10010.20 - Adoption.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 43 Public Lands: Interior 2 2012-10-01 2012-10-01 false Adoption. 10010.20 Section 10010.20 Public Lands: Interior Regulations Relating to Public Lands (Continued) UTAH RECLAMATION MITIGATION AND... Environmental Assessments § 10010.20 Adoption. (a) An EA prepared for a proposal before the Commission...

  7. 43 CFR 10010.20 - Adoption.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 43 Public Lands: Interior 2 2013-10-01 2013-10-01 false Adoption. 10010.20 Section 10010.20 Public Lands: Interior Regulations Relating to Public Lands (Continued) UTAH RECLAMATION MITIGATION AND... Environmental Assessments § 10010.20 Adoption. (a) An EA prepared for a proposal before the Commission...

  8. 43 CFR 10010.20 - Adoption.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 43 Public Lands: Interior 2 2014-10-01 2014-10-01 false Adoption. 10010.20 Section 10010.20 Public Lands: Interior Regulations Relating to Public Lands (Continued) UTAH RECLAMATION MITIGATION AND... Environmental Assessments § 10010.20 Adoption. (a) An EA prepared for a proposal before the Commission...

  9. A Research and Development Adoption Model

    ERIC Educational Resources Information Center

    Hull, Ronald E.

    1974-01-01

    An elaboration of the adoption phase of the Clark and Guba R and D model. A brief discussion of the normative structures of the organizations and organizational boundary permeability provides the rationale for a set of suggested procedures for adoption of innovations at the school building level. (Author)

  10. Fuzzy Cognitive Map Modelling Educational Software Adoption

    ERIC Educational Resources Information Center

    Hossain, Sarmin; Brooks, Laurence

    2008-01-01

    Educational software adoption across UK secondary schools is seen as unsatisfactory. Based on stakeholders' perceptions, this paper uses fuzzy cognitive maps (FCMs) to model this adoption context. It discusses the development of the FCM model, using a mixed-methods approach and drawing on participants from three UK secondary schools. The study…

  11. Adoption of Improved Agricultural Practices in Uruguay.

    ERIC Educational Resources Information Center

    Rucks, Carlos Alberto

    Conducted in Uruguay during 1965-68, this study compared adoption rates for selected agricultural practices between one area which received an extension program and one which did not; and sought relationships between selected characteristics of individual farmers and the adoption of new practices. Data came from interviews with 69 experimental and…

  12. 32 CFR 584.4 - Adoption proceedings.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... situations were a soldier is trying to adopt a child. It applies to those situations where another person is trying to adopt a legitimate or illegitimate child of a soldier. A child born in or out of wedlock... has stated that he or she is not the natural parent of the child. (v) Since the soldier is not...

  13. Adopting the Caregiver Role: A Family Legacy.

    ERIC Educational Resources Information Center

    Piercy, Kathleen W.; Chapman, Jeffery G.

    2001-01-01

    A qualitative study was done to investigate how adult children become caregivers to older parents with functional impairments and what roles their own children adopt in their family's care arrangement. Interviews revealed five influences on children and grandchildren's adoption of caregiver roles: expectations; family rules; religious training;…

  14. Conservation Tillage: Monitoring Adoption with Satellite Imagery

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Conservation tillage is a commonly adopted best management practice for improving soil quality and reducing erosion. However, there are currently no methods in place to monitor conservation tillage adoption at the watershed scale. The primary objective of this study was to evaluate the utility of ...

  15. 76 FR 68613 - National Adoption Month, 2011

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-04

    ... Sig.) [FR Doc. 2011-28839 Filed 11-3-11; 11:15 am] Billing code 3295-F2-P ... Documents#0;#0; ] Proclamation 8744 of November 1, 2011 National Adoption Month, 2011 By the President of... basic support, and still more children abroad live without families. During National Adoption Month,...

  16. 78 FR 66609 - National Adoption Month, 2013

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-05

    .... (Presidential Sig.) [FR Doc. 2013-26669 Filed 11-4-13; 11:15 am] Billing code 3295-F4 ... Documents#0;#0; ] Proclamation 9049 of October 31, 2013 National Adoption Month, 2013 By the President of... million children and teenagers. During National Adoption Month, we celebrate these families and...

  17. 77 FR 66517 - National Adoption Month, 2012

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-06

    ... Sig.) [FR Doc. 2012-27190 Filed 11-5-12; 8:45 am] Billing code 3295-F3 ... Documents#0;#0; ] Proclamation 8896 of November 1, 2012 National Adoption Month, 2012 By the President of... knowing the love and protection of a permanent family. During National Adoption Month, we give voice...

  18. Nurturing Development of Foster and Adopted Children

    ERIC Educational Resources Information Center

    Nowak-Fabrykowski, Krystyna Teresa

    2015-01-01

    The goal of this study is to investigate early childhood teachers' perspective of teaching foster and adopted children. The main purpose is to seek suggestions how teachers can nurture the development of foster and adopted children. A 6 question survey was sent to 44 teachers pursuing graduate studies in early childhood education. Of this 50%…

  19. States Adopt Standards at Fast Clip

    ERIC Educational Resources Information Center

    Gewertz, Catherine

    2010-01-01

    Nearly half the states have adopted a new set of common academic standards, barely a month after their final release and, in most cases, with little opposition. As of July 9, 23 states had decided to replace their mathematics and English/language arts standards with the common set. Another flurry of adoptions is expected by Aug. 2, since the $4…

  20. Wrongful Adoption: Law, Policy and Practice.

    ERIC Educational Resources Information Center

    Freundlich, Madelyn; Peterson, Lisa

    The past decade has seen an increase in cases where adoptive parents fail to receive accurate or complete information about a child's physical, emotional, or developmental problems or about the child's birth family and history. In these cases adoptive parents are confronted with extremely expensive medical care or mental health care. This…

  1. Faculty Adoption of Active Learning Classrooms

    ERIC Educational Resources Information Center

    Van Horne, Sam; Murniati, Cecilia Titiek

    2016-01-01

    Although post-secondary educational institutions are incorporating more active learning classrooms (ALCs) that support collaborative learning, researchers have less often examined the cultural obstacles to adoption of those environments. In this qualitative research study, we adopted the conceptual framework of activity theory to examine the…

  2. [The ageing immune system].

    PubMed

    Djukic, M; Nau, R; Sieber, C

    2014-10-01

    The aging of the immune system, also called immunosenescence, contributes to the increased morbidity and mortality from infections, autoimmune diseases and cancer as well as to the low efficacy of vaccination in elderly persons. Immunosenescence is characterized by a decrease in cell-mediated immune function and by reduced humoral immune responses caused by age-related changes in the innate immune system and age-dependent defects in T-and B-cell function. This paper gives an overview of the most important modifications in the different compartments of the immune system during the ageing process.

  3. [The ageing immune system].

    PubMed

    Djukic, M; Nau, R; Sieber, C

    2014-10-01

    The aging of the immune system, also called immunosenescence, contributes to the increased morbidity and mortality from infections, autoimmune diseases and cancer as well as to the low efficacy of vaccination in elderly persons. Immunosenescence is characterized by a decrease in cell-mediated immune function and by reduced humoral immune responses caused by age-related changes in the innate immune system and age-dependent defects in T-and B-cell function. This paper gives an overview of the most important modifications in the different compartments of the immune system during the ageing process. PMID:25254392

  4. Mutual Interference between Cytomegalovirus and Reconstitution of Protective Immunity after Hematopoietic Cell Transplantation

    PubMed Central

    Reddehase, Matthias J.

    2016-01-01

    Hematopoietic cell transplantation (HCT) is a therapy option for aggressive forms of hematopoietic malignancies that are resistant to standard antitumoral therapies. Hematoablative treatment preceding HCT, however, opens a “window of opportunity” for latent Cytomegalovirus (CMV) by releasing it from immune control with the consequence of reactivation of productive viral gene expression and recurrence of infectious virus. A “window of opportunity” for the virus represents a “window of risk” for the patient. In the interim between HCT and reconstitution of antiviral immunity, primarily mediated by CD8+ T cells, initially low amounts of reactivated virus can expand exponentially, disseminate to essentially all organs, and cause multiple organ CMV disease, with interstitial pneumonia (CMV-IP) representing the most severe clinical manifestation. Here, I will review predictions originally made in the mouse model of experimental HCT and murine CMV infection, some of which have already paved the way to translational preclinical research and promising clinical trials of a preemptive cytoimmunotherapy of human CMV disease. Specifically, the mouse model has been pivotal in providing “proof of concept” for preventing CMV disease after HCT by adoptive transfer of preselected, virus epitope-specific effector and memory CD8+ T cells bridging the critical interim. However, CMV is not a “passive antigen” but is a pathogen that actively interferes with the reconstitution of protective immunity by infecting bone marrow (BM) stromal cells that otherwise form niches for hematopoiesis by providing the structural microenvironment and by producing hematopoietically active cytokines, the hemopoietins. Depending on the precise conditions of HCT, reduced homing of transplanted hematopoietic stem- and progenitor cells to infected BM stroma and impaired colony growth and lineage differentiation can lead to “graft failure.” In consequence, uncontrolled virus spread

  5. Different effects of paternal trans-generational immune priming on survival and immunity in step and genetic offspring

    PubMed Central

    Eggert, Hendrik; Kurtz, Joachim; Diddens-de Buhr, Maike F.

    2014-01-01

    Paternal trans-generational immune priming, whereby fathers provide immune protection to offspring, has been demonstrated in the red flour beetle Tribolium castaneum exposed to the insect pathogen Bacillus thuringiensis. It is currently unclear how such protection is transferred, as in contrast to mothers, fathers do not directly provide offspring with a large amount of substances. In addition to sperm, male flour beetles transfer seminal fluids in a spermatophore to females during copulation. Depending on whether paternal trans-generational immune priming is mediated by sperm or seminal fluids, it is expected to either affect only the genetic offspring of a male, or also their step offspring that are sired by another male. We therefore conducted a double-mating experiment and found that only the genetic offspring of an immune primed male show enhanced survival upon bacterial challenge, while phenoloxidase activity, an important insect immune trait, and the expression of the immune receptor PGRP were increased in all offspring. This indicates that information leading to enhanced survival upon pathogen exposure is transferred via sperm, and thus potentially constitutes an epigenetic effect, whereas substances transferred with the seminal fluid could have an additional influence on offspring immune traits and immunological alertness. PMID:25355479

  6. General recommendations on immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP).

    PubMed

    Kroger, Andrew T; Atkinson, William L; Marcuse, Edgar K; Pickering, Larry K

    2006-12-01

    This report is a revision of General Recommendations on Immunization and updates the 2002 statement by the Advisory Committee on Immunization Practices (ACIP) (CDC. General recommendations on immunization: recommendations of the Advisory Committee on Immunization Practices and the American Academy of Family Physicians. MMWR 2002;51[No. RR-2]). This report is intended to serve as a general reference on vaccines and immunization. The principal changes include 1) expansion of the discussion of vaccination spacing and timing; 2) an increased emphasis on the importance of injection technique/age/body mass in determining appropriate needle length; 3) expansion of the discussion of storage and handling of vaccines, with a table defining the appropriate storage temperature range for inactivated and live vaccines; 4) expansion of the discussion of altered immunocompetence, including new recommendations about use of live-attenuated vaccines with therapeutic monoclonal antibodies; and 5) minor changes to the recommendations about vaccination during pregnancy and vaccination of internationally adopted children, in accordance with new ACIP vaccine-specific recommendations for use of inactivated influenza vaccine and hepatitis B vaccine. The most recent ACIP recommendations for each specific vaccine should be consulted for comprehensive discussion. This report, ACIP recommendations for each vaccine, and other information about vaccination can be accessed at CDC's National Center for Immunization and Respiratory Diseases (proposed) (formerly known as the National Immunization Program) website at http//:www.cdc.gov/nip.

  7. National decision-making on adopting new vaccines: a systematic review.

    PubMed

    Burchett, H E D; Mounier-Jack, S; Griffiths, U K; Mills, A J

    2012-05-01

    In recent years numerous new vaccines have been developed, offering potential reductions in the morbidity and mortality caused by a range of diseases. This has led to increased interest in decision-making about the adoption of new vaccines into national immunization programmes. This paper aims to systematically review the literature on national decision-making around the adoption of new vaccines. A thematic framework was developed inductively through analysis of the vaccine adoption decision-making frameworks included in the review. This thematic framework was then applied to the remaining studies included in the review. In total, 85 articles were included in the review: 39 articles describing examples of vaccine adoption decision-making, 26 presenting vaccine decision-making frameworks, 21 empirical articles of decision-making relating to vaccine adoption and 19 theoretical essays. An analysis of vaccine adoption decision-making frameworks identified nine broad categories of criteria: the importance of the health problem; vaccine characteristics; immunization programme considerations; acceptability; accessibility, equity and ethics; financial/economic issues; impact; alternative interventions and the decision-making process. The quality of the empirical studies was varied. Although some of the issues included in the frameworks were similar to those considered in the studies, there were also some notable differences. On the whole, the frameworks were more comprehensive than the studies, including a greater range of criteria. The existing literature provides a good foundation for further research into vaccine adoption decision-making. The current review, in pulling together what is already known and by identifying strengths, weaknesses and gaps in the existing evidence base, aims to encourage a more focused and rigorous approach to the topic in future. This could help to identify the most appropriate ways to develop vaccine adoption decision-making, so as to improve

  8. [International adoption: children's health risk evolution].

    PubMed

    Dartiguenave, C

    2012-05-01

    The socioeconomic and sanitary conditions in many countries make it necessary to weigh as precisely as possible the uncertainties which might affect the health of internationally adopted children, which is one of the key drivers to adoption decision. Indeed, health troubles are more and more frequent among children proposed by countries, at a time when there are fewer children to be adopted. Hence the institutions and the actors in the field of international adoption are compelled to frequently update their professional practices, so as to cope both with the declining offer for adoptable children and with the increasing pressure from the birth countries of children to make host countries adopt children with high age or with special needs. It also requires from the administrations the will to provide better initial information and to implement the demand for an agreement. Meanwhile, in spite of those growing constraints, adopting families have been more and more risk adverse during the latest decades, this being a common trend in our developed countries.

  9. Parallel Process Issues for Lesbian and Gay Adoptive Parents and Their Adopted Children

    ERIC Educational Resources Information Center

    Matthews, John D.; Cramer, Elizabeth P.

    2005-01-01

    Gays and lesbians, both single and coupled, are increasingly turning to adoption to create or expand their families. This manuscript specifically addresses the continuing needs of adoptees and adoptive parents by exploring key issues in the life course of gays and lesbians and their adopted children, and identifying potential parallel development…

  10. 20 CFR 404.733 - Evidence you are the legally adopting parent or legally adopted child.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... or legally adopted child. 404.733 Section 404.733 Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL OLD-AGE, SURVIVORS AND DISABILITY INSURANCE (1950- ) Evidence Evidence for Child's and Parent's Benefits § 404.733 Evidence you are the legally adopting parent or legally adopted child. If you are...

  11. Factors Influencing the Adoption Decision: An Analysis of Adopters and Nonadopters.

    ERIC Educational Resources Information Center

    King, Robert N.; Rollins, Timothy

    1995-01-01

    An agricultural innovation (nitrogen testing) had been used by 127 of a sample of 220 farmers. Adoption of the technique was influenced by information and change agents' attitudes. Adopters were also motivated by cost savings. Both adopters and nonadopters either did not have or use soil sampling skills needed to perform the test correctly.…

  12. Open Adoption of Infants: Adoptive Parents' Perceptions of Advantages and Disadvantages.

    ERIC Educational Resources Information Center

    Siegel, Deborah H.

    1993-01-01

    Conducted qualitative study of adoptive parents' (n=21 couples) reactions to recent open adoptions of their infants. Findings indicated overwhelmingly positive feelings about open adoption. Respondents often noted that issue of openness was eclipsed by other concerns: coping with infertility, finding a baby, dealing with personnel, and dealing…

  13. 20 CFR 404.733 - Evidence you are the legally adopting parent or legally adopted child.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... or legally adopted child. 404.733 Section 404.733 Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL OLD-AGE, SURVIVORS AND DISABILITY INSURANCE (1950- ) Evidence Evidence for Child's and Parent's Benefits § 404.733 Evidence you are the legally adopting parent or legally adopted child. If you are...

  14. Cultural Tourism in Transnational Adoption: "Staged Authenticity" and Its Implications for Adopted Children

    ERIC Educational Resources Information Center

    Quiroz, Pamela Anne

    2012-01-01

    The discursive practices of adoptive parents in two online transnational adoption forums (2006-2008) and observations of five international adoption workshops suggest that what Heather Jacobson described as "culture keeping", the cultural socialization of children that retains a sense of native group identity, is more aptly characterized as…

  15. Korean Adoptee Identity: Adoptive and Ethnic Identity Profiles of Adopted Korean Americans

    ERIC Educational Resources Information Center

    Beaupre, Adam J.; Reichwald, Reed; Zhou, Xiang; Raleigh, Elizabeth; Lee, Richard M.

    2015-01-01

    Adopted Korean adolescents face the task of grappling with their identity as Koreans and coming to terms with their adoptive status. In order to explore these dual identities, the authors conducted a person-centered study of the identity profiles of 189 adopted Korean American adolescents. Using cluster analytic procedures, the study examined…

  16. A Study of Self-Esteem in Adopted Non-adopted Adolescents.

    ERIC Educational Resources Information Center

    Steward, Robbie J.; Lynn, Betty Jane

    This study tested the hypothesis that adopted adolescents have lower self-esteem than do non-adopted adolescents. Male and female students (N=159) between the ages of 18 and 22 were conveniently sampled from college undergraduate populations. Forty-four of the participants reported adoptive status. Each participant completed the Coopersmith…

  17. Sequential Immune Responses: The Weapons of Immunity

    PubMed Central

    Mills, Charles D.; Ley, Klaus; Buchmann, Kurt; Canton, Johnathan

    2016-01-01

    Sequential immune responses (SIR) is a new model that describes what ‘immunity’ means in higher animals. Existing models, such as self/nonself discrimination or danger, focus on how immune responses are initiated. However, initiation is not protection. SIR describes the actual immune responses that provide protection. SIR resulted from a comprehensive analysis of the evolution of immune systems that revealed that several very different types of host innate responses occur (and at different tempos) which together provide host protection. SIR1 uses rapidly activated enzymes like the NADPH oxidases and is present in all animal cells. SIR2 is mediated by the first ‘immune’ cells: macrophage-like cells. SIR3 evolved in animals like invertebrates and provides enhanced protection through advanced macrophage recognition and killing of pathogens and through other innate immune cells such as neutrophils. Finally, in vertebrates, macrophages developed SIR4: the ability to present antigens to T cells. Though much slower than SIR1–3, adaptive responses provide a unique new protection for higher vertebrates. Importantly, newer SIR responses were added on top of older, evolutionarily conserved functions to provide ‘layers’ of host protection. SIR transcends existing models by elucidating the different weapons of immunity that provide host protection in higher animals. PMID:25871013

  18. Pricing Health Behavior Interventions to Promote Adoption

    PubMed Central

    Ribisl, Kurt M.; Leeman, Jennifer; Glasser, Allison M.

    2015-01-01

    The relatively high cost of delivering many public health interventions limits their potential for broad public impact by reducing their likelihood of adoption and maintenance over time. Practitioners identify cost as the primary factor for which interventions they select to implement, but researchers rarely disseminate cost information or consider its importance when developing new interventions. A new approach is proposed, whereby intervention developers assess what individuals and agencies adopting their interventions are willing to pay and then design interventions that are responsive to this price range. The ultimate goal is to develop effective and affordable interventions, called lean interventions, which are widely adopted and have greater public health impact. PMID:24842743

  19. Intercountry adoption: a review of the evidence.

    PubMed

    Tizard, B

    1991-07-01

    Studies of the outcome of intercountry adoption are reviewed in the context of its history and politics. Intercountry adoption is a post-World War II phenomenon, and has become largely a service for childless couples in the West. Many Third World countries, and some Western social workers, are bitterly opposed to the practice, on both political and psychological grounds. Outcome studies have produced results similar to those found in studies of incountry adoption, although, to date, insufficient attention has been paid to issues of identity and racism. The policy implications of these studies will depend on political considerations, as well as the research evidence.

  20. Effect of feeding whole compared with cell-free colostrum on calf immune status: The neonatal period.

    PubMed

    Langel, S N; Wark, W A; Garst, S N; James, R E; McGilliard, M L; Petersson-Wolfe, C S; Kanevsky-Mullarky, I

    2015-06-01

    Mortality and decreased weight gain resulting from infection and disease in dairy calves are problems within the dairy industry. The bovine neonate relies solely on colostrum to acquire antibodies through passive transfer. To date, colostrum quality is determined by the concentration of antibodies. However, proteins and cells in the colostrum might also enhance immune development in the neonate. To determine the effect of maternal colostral immune cells on calf health and immune status, maternal colostrum was fed either fresh or after lysis of cells by flash-freezing in liquid nitrogen. Thirty-seven female Holstein and Jersey dairy calves were fed 4 quarts total of whole colostrum (WC) or cell-free colostrum (CFC) at birth. Respiratory and fecal scores were measured from birth to d 45 of life. Calf peripheral blood samples were obtained before and after feeding colostrum as well as on d 1, 3, 7, 14, 21, and 28 of life. Peripheral blood mononuclear cells were collected and analyzed for cellular parameters by flow cytometry. Total respiratory scores were greater in CFC-fed calves compared with WC-fed calves on d 38 of life. There were fewer CD4+ T cells and CD4+CD62L+CD45RO- T cells on d 1 and fewer CD4+CD62L+CD45RO+ T cells on d 1 and 3 in CFC-fed calves compared with WC-fed calves. Compared with WC-fed calves, CFC-fed calves had a greater percentage of CD4+CD62L-CD45RO+ T cells on d 0.25, 1, 3, and 7, and a greater percentage of monocytes on d 7. Our data suggest that colostral cells adoptively transfer and enhance neonatal immunity during the first month of life. PMID:25795487