Role of CD25+ dendritic cells in the generation of Th17 autoreactive T cells in autoimmune experimental uveitis.

Role of CD25+ dendritic cells in the generation of Th17 autoreactive T cells in autoimmune experimental uveitis.
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DOI:
10.4049/jimmunol.1200109
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发表时间:
2012-06-01
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Sun D
Sun D
中科院分区:
其他
文献类型:
--
作者:
Liang D;Zuo A;Shao H;Born WK;O'Brien RL;Kaplan HJ;Sun D

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在本研究中,我们发现体内注射抗CD25抗体(PC61)降低了葡萄膜生成多肽IRBP1-20免疫的C57BL/6(B6)小鼠的Th17反应,同时增强了自身反应的Th1反应。Th1 7反应减弱与表达CD11c+CD3、−CD2 5+的树突状细胞(DC)亚群减少和γδT细胞增殖减少密切相关。我们证明,CD2 5+DC亚群的消融导致γδT细胞的激活和扩张减少,导致IL-17+IRBP特异性T细胞的激活减少。我们的结果表明,自身免疫性疾病中Th1 7反应的增强与表达CD2 5的DC亚群的出现有关,抗CD2 5抗体治疗小鼠导致许多免疫细胞类型的功能改变,即DC和γδT细胞,以及CD2 5+αβTcr+调节性T细胞。
In the present study, we showed that in vivo administration of an anti-CD25 antibody (PC61) decreased the Th17 response in C57BL/6 (B6) mice immunized with the uveitogenic peptide IRBP1–20, while enhancing the autoreactive Th1 response. The depressed Th17 response was closely associated with decreased numbers of a splenic dendritic cell (DC) subset expressing CD11c+CD3−CD25+ and decreased expansion of γδ T cells. We demonstrated that ablation of the CD25+ DC subset accounted for the decreased activation and the expansion of γδ T cells, leading to decreased activation of IL-17+ IRBP-specific T cells. Our results show that an enhanced Th17 response in an autoimmune disease is associated with the appearance of a DC subset expressing CD25 and that treatment of mice with anti-CD25 antibody causes functional alterations in a number of immune cell types, namely DCs and γδ T cells, in addition to CD25+αβTCR+ regulatory T cells.
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