A short course of high-dose IL-2 starting on the day of BMT can up-regulate the SOCS-3 expression of donor naive CD4+ T cells. The proliferation and Th1-type polarization of donor naive CD4+ T cells inducibly expressing SOCS-3 is inhibited, which inhibits immunity to allogeneic antigen and aGVHD. Our animal experiment provided strong support for this hypothesis. Clearly, IL-2 pre-incubation can inhibit fully MHC-mismatched mice fatal aGVHD; but
donor lymphocytes incubated with IL-2 for 4 h injected immediately into recipients did not inhibit aGVHD. If the lymphocytes inducibly expressing SOCS-3 were stimulated with allogeneic antigen for 72 h, Ruxolitinib mw aGVHD could be inhibited significantly. A possible explanation is that it needs time for donor lymphocytes to receive the antigen presented by host APC, but SOCS-3 is a short-lived gene product induced in lymphocytes by IL-2. PF-02341066 concentration SOCS-3 could not generate inhibition to aGVHD unless the lymphocytes inducibly expressing SOCS-3 receive allogeneic antigen
in time. Methods of inhibiting aGVHD, such as glucocorticosteroid, anti-thymocyte globulin, cyclosporin A and methylaminopterin, inhibit the whole immune system, and this can lead to the inhibition of graft-versus-tumour effects and serious infections. The aim of this study was to adjust the direction of polarization of Th and to inhibit excessive proliferation during aGVHD; the animal experimental results show the effectiveness of our aim. IL-2 pre-incubation can prevent aGVHD through up-regulating the expression
of SOCS-3 and inhibiting the proliferation of Th1-type polarization of naive CD4+ T cells. oxyclozanide Hopefully, these will provide new pathways for the inhibition of aGVHD. This paper was supported by the Great Biology and Medicine Foundation of Key Problems in Science and the Technology of Shanghai Science and Technology Committee (no. 06DZ19013). We acknowledge Dr Wan Yin (Department of immunology, Shanghai Medical College, Fudan University), who supported us very much during the initiation of our work. None. “
“Chronic granulomatous disease (CGD) is a primary immunodeficiency defined by mutations in the NADPH oxidase complex leading to reduced superoxide production, increased susceptibility to infection, chronic inflammation, and recurring abscess and granuloma formation. Here, we found that CGD mice were hyperresponsive to abscess-inducing T-cell-dependent carbohydrate antigens (glycoantigens) due to a ten-fold increase in NO production within APCs, which is known to be necessary for glycoantigen presentation on MHC class II. CGD mice exhibited increased Th1 pro-inflammatory T-cell responses in vitro and in vivo, characterized by more severe abscess pathology. This phenotype was also seen in WT animals following adoptive transfer of neutrophil-depleted APCs from CGD animals, demonstrating that this phenotype was independent of neutrophil and T-cell defects.