Natural recovery and protection from autoimmune encephalomyelitis:: Contribution of CD4+CD25+ regulatory cells within the central nervous system
Natural recovery and protection from autoimmune encephalomyelitis:: Contribution of CD4+CD25+ regulatory cells within the central nervous system
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DOI：
10.4049/jimmunol.175.5.3025
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发表时间：
2005-09-01
影响因子：
4.4
通讯作者：
Anderton, SM
中科院分区：
文献类型：
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作者：
McGeachy, MJ;Stephens, LA;Anderton, SM
自身免疫性疾病的免疫调节可在两个部位发挥作用：次级淋巴器官或靶器官本身。在这项研究中，我们使用小鼠实验性自身免疫性脑脊髓炎(EAE)来研究中枢神经系统内自身免疫病理的自然分解。恢复与中枢神经系统内产生IL-10的CD4(+)CD25(+)T细胞的积累有关。这些CD4(+)CD25(+)细胞在恢复期代表了中枢神经系统中多达三分之一的CD4(+)细胞，它们是FoxP3(+)，并表达与调节细胞相关的其他标志(CTLA-4、GITR和α(E)β7)，它们在体外具有调节功能。CD25(+)细胞的耗尽抑制了EAE的自然恢复。此外，恢复后CD25(+)细胞的耗尽消除了在该模型中观察到的对再次诱导EAE的抵抗力。此外，被动转移少量CNS来源的CD4(+)CD25(+)细胞可以保护受体小鼠免受EAE的侵袭。这些数据首次表明，在靶器官内，CD4(+)CD25(+)调节性T细胞直接参与自身免疫性疾病的自然解决。
Immune regulation of autoimmune disease can function at two sites: at the secondary lymphoid organs or in the target organ itself. In this study, we investigated the natural resolution of autoimmune pathology within the CNS using murine experimental autoimmune encephalomyelitis (EAE). Recovery correlates with the accumulation of IL-10-producing CD4(+)CD25(+) T cells within the CNS. These CD4(+)CD25(+) cells represent as many as one in three of CD4(+) cells in the CNS during recovery, they are FoxP3(+) and express other markers associated with regulatory cells (CTLA-4, GITR, and alpha(E)beta 7), and they have regulatory function ex vivo. Depletion of CD25(+) cells inhibits the natural recovery from EAE. Also, depletion of CD25(+) cells after recovery removes the resistance to reinduction of EAE observed in this model. Furthermore, passive transfer of CNS-derived CD4(+)CD25(+) cells in low numbers provides protection from EAE in recipient mice. These are the first data demonstrating the direct involvement of CD4(+)CD25(+) regulatory T cells in the natural resolution of autoimmune disease within the target organ.