Characterization of IL-17+ interphotoreceptor retinoid-binding protein-specific T cells in experimental autoimmune uveitis
Characterization of IL-17+ interphotoreceptor retinoid-binding protein-specific T cells in experimental autoimmune uveitis
复制标题
DOI：
10.1167/iovs.07-0251
复制
发表时间：
2007-09-01
影响因子：
4.4
通讯作者：
Sun, Deming
中科院分区：
文献类型：
--
作者：
Peng, Yong;Han, Gencheng;Sun, Deming
目的.本研究旨在确定IL-17（+）T细胞是否存在于CD 4和CD 8感光细胞间类维生素A结合蛋白（IRBP）特异性T细胞中，并确定抗原特异性和非特异性IL-17（+）T细胞在实验性自身免疫性葡萄膜炎（EAU）发病机制中的作用。用致葡萄膜肽IRBP 1 -20免疫B6小鼠。分离体内致敏的T细胞并用免疫肽刺激。评估T细胞的IFN-γ和IL- 17的细胞内表达，并测定活化的T细胞的致病活性。自身反应性IRBP特异性CD 8 T细胞亚群表达IL-17。当用IL- 23扩增时，IRBP特异性T细胞优先表达IL-17，而当用IL-2培养T细胞时，IFN-γ表达细胞占优势。重要的是，两种扩增的T细胞群体都是葡萄膜炎原性的。此外，IL-23促进抗原特异性和非抗原特异性IL-17（+）T细胞的扩增，而TGF-β和IL-6仅作用于非抗原特异性IL-17（+）T细胞。只有抗原特异性IL-17（+）T细胞是葡萄膜原性的。CFA和百日咳毒素（PTX）的分枝杆菌成分在体内以及Toll样受体的连接在体外均能显著增加自身反应性IL-17（+）T细胞的活化。IL-17（+）T细胞可在活化的自身反应性T细胞和旁观者T细胞中检测到，并可能在EAU的发病机制中起主要作用。
PURPOSE. The aims of this study were to determine whether IL-17(+) T cells were present in CD4 and CD8 interphotoreceptor retinoid-binding protein ( IRBP)-specific T cells and to determine the role of antigen-specific and nonspecific IL-17 (+) T cells in the pathogenesis of experimental autoimmune uveitis (EAU).METHODS. B6 mice were immunized with uveitogenic peptide IRBP1-20. In vivo-primed T cells were separated and stimulated with the immunizing peptide. Intracellular expression of IFN-gamma and IL- 17 by the T cells was assessed, and the pathogenic activity of the activated T cells was determined.RESULTS. A subset of autoreactive IRBP-specific CD8 T cells expressed IL-17. IRBP-specific T cells preferentially expressed IL-17 when expanded by IL- 23, whereas IFN-gamma -expressing cells were dominant when the T cells were cultured with IL-2. Importantly, both expanded T-cell populations were uveitogenic. In addition, IL-23 promoted the expansion of antigenspecific and non-antigen-specific IL-17(+) T cells, whereas TGF-beta and IL-6 acted only on non-antigen- specific IL-17(+) T cells. Only the antigen-specific IL-17(+) T cells were uveitogenic. The activation of autoreactive IL-17(+) T cells was markedly increased in vivo by the mycobacterial component of CFA and pertussis toxin ( PTX) and in vitro by the ligation of Toll-like receptors.CONCLUSIONS. IL-17(+) T cells can be readily detected among activated autoreactive and bystander T cells and may play a major role in the pathogenesis of EAU.