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• W1876464564 abstract "Tolerogenic dendritic cells (DC) play an important role in maintaining peripheral T cell tolerance in steady-state conditions through induction of anergic, IL-10-producing T cells with suppressive properties. ICOS, an activation-induced member of the CD28 family on T cells, is involved in the induction of IL-10, which itself could contribute to induction of anergy and development of suppressive T cells. Therefore, we analyzed the functional role of ICOS in the differentiation process of human CD4(+) T cells upon their interaction with tolerogenic DC. We compared the functional properties of CD4(+) T cells from healthy volunteers and ICOS-deficient patients after stimulation with tolerogenic DC. We report that induction of T cell anergy and suppressive capacity is completely blocked after knockdown of ICOS expression in T cells as well as after blocking of ICOS-ICOS ligand interaction in DC/T cell cocultures. Moreover, CD4(+) T cells from ICOS-deficient patients were completely resistant to anergy induction and differentiation into suppressive T cells even after supplementation of IL-10. Furthermore, ICOS/ICOS ligand interaction stabilizes IL-10R expression on T cells and thus renders them sensitive to IL-10 effects. Taken together, these results indicate a crucial role for ICOS in the induction of peripheral tolerance maintained by tolerogenic DC mediated mostly via an IL-10-independent mechanism." @default.
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• W1876464564 date "2009-03-15" @default.
• W1876464564 modified "2023-10-06" @default.
• W1876464564 title "The Role of ICOS in Directing T Cell Responses: ICOS-Dependent Induction of T Cell Anergy by Tolerogenic Dendritic Cells" @default.
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• W1876464564 doi "https://doi.org/10.4049/jimmunol.0802733" @default.
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