Major role of gamma delta T cells in the generation of IL-17+ uveitogenic T cells.
Major role of gamma delta T cells in the generation of IL-17+ uveitogenic T cells.
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DOI：
10.4049/jimmunol.0900241
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发表时间：
2009-07-01
期刊：
影响因子：
--
通讯作者：
Sun D
中科院分区：
文献类型：
--
作者：
Cui Y;Shao H;Lan C;Nian H;O'Brien RL;Born WK;Kaplan HJ;Sun D
我们发现，在TH17极化条件下，用葡萄膜源性视黄醇结合蛋白多肽(IRBP1-20)免疫C57BL/6小鼠的光感受器间视黄醇结合蛋白(IRBP)特异性T细胞的体外激活与表达γδTCRT细胞的增加有关。我们还发现，用IRBP1-20免疫的C57BL/6小鼠的高纯度αβ或γδT细胞在体外暴露于免疫抗原后只产生少量的IL-17，而相同的T细胞混合后产生的IL-17显著增加。与野生型C57BL/6小鼠相比，C57BL/6基因背景的IRBP免疫TCR-γ−/−小鼠诱导的T细胞产生IL-17的量显著减少，并显著降低了实验性自身免疫性葡萄膜炎的诱导能力。然而，用IRBP免疫的C57BL/6小鼠的少量γ−/−T细胞在免疫前重建TCR-γδ小鼠，恢复了其IRBP特异性T细胞的致病能力，并极大地促进了受体小鼠IL-17+T细胞的产生。我们的研究表明，γδT细胞在产生和激活产生IL-17的自身反应性T细胞中起重要作用，并在实验性自身免疫性葡萄膜炎的发病机制中发挥重要作用。
We show that in vitro activation of interphotoreceptor retinoid-binding protein (IRBP)-specific T cells from C57BL/6 mice immunized with an uveitogenic IRBP peptide (IRBP1–20) under TH17-polarizing conditions is associated with increased expansion of T cells expressing the γδ TCR. We also show that highly purified αβ or γδ T cells from C57BL/6 mice immunized with IRBP1–20 produced only small amounts of IL-17 after exposure to the immunizing Ag in vitro, whereas a mixture of the same T cells produced greatly increased amounts of IL-17. IRBP-induced T cells from IRBP-immunized TCR-γ−/−mice on the C57BL/6 genetic background produced significantly lower amounts of IL-17 than did wild-type C57BL/6 mice and had significantly decreased experimental autoimmune uveitis-inducing ability. However, reconstitution of the TCR-γ−/−mice before immunization with a small number of γδ T cells from IRBP-immunized C57BL/6 mice restored the disease-inducing capability of their IRBP-specific T cells and greatly enhanced the generation of IL-17+ T cells in the recipient mice. Our study suggests that γδ T cells are important in the generation and activation of IL-17-producing autoreactive T cells and play a major role in the pathogenesis of experimental autoimmune uveitis.
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影响因子：
4.4
作者：
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作者：
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