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• W1970194048 abstract "Human vascular endothelial cells (EC) are able to present antigen and to activate T lymphocytes. IL-10, a pleiotropic, mainly immunosuppressive cytokine, is known to inhibit antigen uptake and presentation. Its effects on EC have not yet been investigated in detail. We have previously demonstrated IL-10 receptor expression and effective signaling via STAT-3 in human umbilical vein EC (HUVEC). In a novel T cell proliferation assay utilizing HUVEC transgenic for Fcγ receptor type II (CD32) the effects of IL-10 on EC-dependent T cell activation were investigated. This system allows the study of endothelial costimulation independent of alloantigen uptake and presentation after binding of mitogenic anti-CD3 antibody CD32 on EC. Pretreatment of HUVEC with IL-10 resulted in a dose-dependent inhibition of CD4+ or CD8+ T cell proliferation which reached 70% inhibition with 10ng/ml of IL-10. If IL-10 was removed after pre-treatment similar levels of inhibition were reached, however a significantly smaller inhibition could be shown for addition of IL-10 at the beginning of T cell costimulation. Altered binding of the comitogenic CD3 antibody, changes in the expression of costimulatory molecules, changes in eNOS expression/NO production and altered IL-12 secretion could be excluded as potential causes of costimulation inhibition. However, we were able to show significant upregulation of SOCS3 (4-fold), a potent negative regulator of cytokine secretion, and de-novo expression of ILT-3, a surface receptor implicated to mediate the suppressive effect of regulatory CD4+CD25+ T cells and CD8+CD28-alloantigen-specific T suppressor cells, by RT-PCR and Western blot analysis. In conclusion, the T cell-stimulatory potential of human EC is suppressed by IL-10 independently of antigen presentation. Regarding kinetics of inhibition as well as upregulation of SOCS-3 and de-novo expression of ILT-3, altered cytokine secretion and cell contact-dependent modulation of costimulation seem to be most likely the underlying mechanisms of this observation." @default.
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• W1970194048 date "2004-02-01" @default.
• W1970194048 modified "2023-09-27" @default.
• W1970194048 title "Human endothelial T cell costimulation is inhibited by interleukin 10 (IL-10) through induction of suppressor of cytokine secretion-3 (SOCS-3) and ILT-3" @default.
• W1970194048 doi "https://doi.org/10.1016/j.healun.2003.11.019" @default.
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