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  • The American Association of Immunologists  (5)
  • 1
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 178, No. 1 ( 2007-01-01), p. 480-488
    Abstract: The FcR common γ-chain (FcRγ) is an essential component of the receptors FcεRI, FcγRI, and FcγRIII, which are expressed on many inflammatory cell types. The role of these receptors in the initiation or maintenance of allergic inflammation has not been well defined. FcRγ-deficient (FcRγ−/−) and control (wild-type (WT)) mice were sensitized and subsequently challenged with OVA. Following sensitization and challenge to OVA, FcRγ-deficient (FcRγ−/−) mice developed comparable levels of IgE and IgG1 as WT mice. However, numbers of eosinophils, levels of IL-5, IL-13, and eotaxin in bronchoalveolar lavage fluid, and mononuclear cell (MNC) proliferative responses to OVA were significantly reduced, as was airway hyperresponsiveness (AHR) to inhaled methacholine. Reconstitution of FcRγ−/− mice with whole spleen MNC from WT mice before sensitization restored development of AHR and the numbers of eosinophils in bronchoalveolar lavage fluid; reconstitution after sensitization but before OVA challenge only partially restored these responses. These responses were also restored when FcRγ−/− mice received T cell-depleted MNC, T and B cell-depleted MNC, or bone marrow-derived dendritic cells before sensitization from FcR+/+ or FcγRIII-deficient but not FcRγ−/− mice. The expression levels of FcγRIV on bone marrow-derived dendritic cells from FcR+/+ mice were found to be low. These results demonstrate that expression of FcRγ, most likely FcγRI, on APCs is important during the sensitization phase for the development of allergic airway inflammation and AHR.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
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    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2007
    detail.hit.zdb_id: 1475085-5
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  • 2
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 194, No. 3 ( 2015-02-01), p. 1357-1363
    Abstract: Chronic graft-versus-host disease (GVHD) is a major cause of late death and morbidity after allogeneic hematopoietic cell transplantation. Recently, in addition to Th2 cells, Th1 and Th17 cells have been shown to contribute to chronic GVHD progression. IL-12 induces Th1 cells and IL-23 plays a role in stabilizing and/or amplifying Th17 cells, as well as in inducing IFN-γ/IL-17 double-producing cells. Because mAb targeting the p40 subunit common to both IL-12 and IL-23 can inhibit both IL-12R and IL-23R-mediated signaling, we investigated the effects of anti-p40 mAb on a well-defined chronic GVHD mice model. Treatment of anti-p40 mAb in allogeneic recipients significantly reduced the severity of clinical and pathological chronic GVHD. Intracellular staining revealed that IFN-γ single-positive (IL-17−) and IFN-γ/IL-17 double-positive cells were suppressed in anti-p40 mAb–treated allogeneic recipients compared with control recipients. The cytokine levels of IFN-γ and IL-17 were also decreased in serum from anti-p40 mAb–treated allogeneic recipients. T-bet expression of donor IL-17+ CD4+ T cells was reduced significantly in anti-p40 mAb–treated recipients, and this reduction in T-bet expression was associated with IL-22 production by donor T cells. These results suggested that anti-p40 mAb attenuated chronic GVHD via suppression of IFN-γ/IL-17–producing cells, and that targeting the IL-12/IL-23 pathway may represent a promising therapeutic strategy for preventing and treating chronic GVHD.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
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    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2015
    detail.hit.zdb_id: 1475085-5
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  • 3
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 174, No. 1 ( 2005-01-01), p. 551-556
    Abstract: NKT cells are a unique immunoregulatory T cell population that produces large amounts of cytokines. We have investigated whether stimulation of host NKT cells could modulate acute graft-vs-host disease (GVHD) in mice. Injection of the synthetic NKT cell ligand α-galactosylceramide (α-GalCer) to recipient mice on day 0 following allogeneic bone marrow transplantation promoted Th2 polarization of donor T cells and a dramatic reduction of serum TNF-α, a critical mediator of GVHD. A single injection of α-GalCer to recipient mice significantly reduced morbidity and mortality of GVHD. However, the same treatment was unable to confer protection against GVHD in NKT cell-deficient CD1d knockout (CD1d−/−) or IL-4−/− recipient mice or when STAT6−/− mice were used as donors, indicating the critical role of host NKT cells, host production of IL-4, and Th2 cytokine responses mediated by donor T cells on the protective effects of α-GalCer against GVHD. Thus, stimulation of host NKT cells through administration of NKT ligand can regulate acute GVHD by inducing Th2 polarization of donor T cells via STAT6-dependent mechanisms and might represent a novel strategy for prevention of acute GVHD.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
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    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2005
    detail.hit.zdb_id: 1475085-5
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  • 4
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 193, No. 5 ( 2014-09-01), p. 2565-2573
    Abstract: Chronic graft-versus-host disease (GVHD) is a major cause of late death and morbidity after allogeneic hematopoietic cell transplantation, but its pathogenesis remains unclear. We investigated the role of the programmed death-1 (PD-1) pathway in chronic GVHD using a well-defined mouse model of B10.D2 (H-2d) donor to BALB/c (H-2d) recipients. PD-1 expression on allogeneic donor T cells was upregulated continuously in chronic GVHD development, whereas PD-L1 expression in host tissues was transiently upregulated and declined to basal levels in the late posttransplant period. Blockade of the PD-1 pathway by anti–PD-1, anti–PD-L1, or anti–PD-L2 mAbs exacerbated clinical and pathologic chronic GVHD. Chimeric mice revealed that PD-L1 expression in host tissues suppressed expansion of IL-17+IFN-γ+ T cells, and that PD-L1 expression on hematopoietic cells plays a role in the development of regulatory T cells only during the early transplantation period but does not affect the severity of chronic GVHD. Administration of the synthetic retinoid Am80 overcame the IL-17+IFN-γ+ T cell expansion caused by PD-L1 deficiency, resulting in reduced chronic GVHD damage in PD-L1−/− recipients. Stimulation of the PD-1 pathway also alleviated chronic GVHD. These results suggest that the PD-1 pathway contributes to the suppression of Th17/Th1-mediated chronic GVHD and may represent a new target for the prevention or treatment of chronic GVHD.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
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    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2014
    detail.hit.zdb_id: 1475085-5
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  • 5
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 169, No. 4 ( 2002-08-15), p. 2164-2171
    Abstract: The development of rapid, efficient, and safe methods for generating Ag-specific T cells is necessary for the clinical application of adoptive immunotherapy. We show that B cells stimulated with CD40 ligand and IL-4 (CD40-B cells) can be efficiently transduced with retroviral vectors encoding a model Ag, CMV tegument protein pp65 gene, and maintain high levels of costimulatory molecules after gene transfer. CTL lines specific for pp65 were readily generated in all four healthy CMV-seropositive donors by stimulating autologous CD8+ T cells with these transduced CD40-B cells, both of which were derived from 10 ml peripheral blood. ELISPOT assays revealed that the CTL lines used multiple HLA alleles as restricting elements. Thus, CD40-B cells transduced retrovirally with Ag-encoding cDNA can be potent APC and facilitate to generate Ag-specific CTL in vitro.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
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    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2002
    detail.hit.zdb_id: 1475085-5
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