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- W2016097810 abstract "Human vascular endothelial cells (EC) are known to present antigen and to activate T lymphocytes. Interleukin 10 (IL-10), a mainly immunosuppressive cytokine, is known to inhibit antigen-uptake and presentation. However, its effects on EC-dependent T cell activation have not been investigated in detail. We have previously demonstrated expression of the IL-10 receptor and effective intracellular signaling via Stat-3 in human umbilical vein EC (HUVEC). In a proliferation assay allowing exclusive study of endothelial costimulation through binding CD3 mAb to CD32 transgenic HUVEC, pre-treatment of HUVEC with IL-10 resulted in a marked dose-dependent inhibition of CD4+ T cell proliferation persisting when IL-10 was removed after 24h pre-treatment. IL-10 pre-incubation of HUVEC resulted in significant reduction of IL-2 and IL-4 levels in coculture supernatants, analysis of T-bet and GATA-3 mRNA expression in CD4 T cells showed no change in Th1/Th2 polarization. Similarly, no effects on endothelial nitric oxide, IL-12, or IL-15 production were seen. Addition of exogenous IL-2 was able to overcome inhibition of proliferation. IL-10 stimulation of EC resulted in significant upregulation of SOCS-3, a potent negative regulator of cytokine secretion, as well as de-novo expression of ILT3, and upregulation of ILT4, two tolerogenic surface receptors implicated in the generation of regulatory T cells. Accordingly, CD4 T cells stimulated with IL-10 pretreated HUVEC showed markedly enhanced IL-10 production indicating an increased fraction of regulatory T cells. In conclusion, the T cell-costimulatory potential of human EC is markedly suppressed by IL-10. Regarding the kinetics of inhibition as well as the upregulation of SOCS-3 and of ILT3/ILT4 by IL-10, multiple mechanisms account for this novel property of IL-10. These include altered cytokine secretion as well as cell contact-dependent modulation of T cell activation involving the generation of regulatory T cells." @default.
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- W2016097810 date "2005-02-01" @default.
- W2016097810 modified "2023-09-29" @default.
- W2016097810 title "Interleukin-10 reduces endothelium-dependent T cell costimulation through upregulation of suppressor of cytokine signaling-3 and immunoglobulin-like transcript 3 and 4" @default.
- W2016097810 doi "https://doi.org/10.1016/j.healun.2004.11.290" @default.
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