Regulatory T cells control autoimmunity in vivo by inducing apoptotic depletion of activated pathogenic lymphocytes
Regulatory T cells control autoimmunity in vivo by inducing apoptotic depletion of activated pathogenic lymphocytes
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DOI：
10.4049/jimmunol.170.6.2985
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发表时间：
2003-03-15
影响因子：
4.4
通讯作者：
Kumar, V
中科院分区：
文献类型：
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作者：
Madakamutil, LT;Maricic, I;Kumar, V
临床自身免疫需要自身反应性T细胞的激活以及外周耐受机制的失败。我们先前鉴定了一种这样的机制，其涉及在MHC背景下识别TCR V β 8.2（+）链衍生肽的调节性T细胞。这种调节如何影响体内介导实验性自身免疫性脑脊髓炎的靶V β 8.2（+）T淋巴细胞的命运仍然未知。本研究使用免疫显微镜和CFSE标记分析证实，体内调节性CD4和CD8 T细胞的扩增导致显性髓鞘碱性蛋白反应性V β 8.2（+）T细胞的凋亡耗竭，但不导致亚显性V β 8.2（+）T细胞的凋亡耗竭。通过这种负反馈机制仅消除活化的T细胞保留了初始V β 8.2（+）T细胞库的剩余部分，同时导致对疾病的保护。这些研究首次明确阐明了髓鞘碱性蛋白特异性致脑炎T细胞在体内受调控后的命运。
Clinical autoimmunity requires both activation of self-reactive T cells as well as a failure-of peripheral tolerance mechanisms. We previously identified one such mechanism that involves regulatory T cells recognizing TCR Vbeta8.2(+) chain-derived peptides in the context of MHC. How this regulation affects the fate of target Vbeta8.2(+) T lymphocytes in vivo that mediate experimental autoimmune encephalomyelitis has remained unknown. The present study using immunoscope and CFSE-labeling analysis demonstrates that the expansion of regulatory CD4 and CD8 T cells in vivo results in apoptotic depletion of the dominant, myelin basic protein-reactive Vbeta8.2(+) T cells, but not subdominant Vbeta8.2(+) T cells. The elimination of only activated T cells by this negative feedback mechanism preserves the remainder of the naive Vbeta8.2(+) T cell repertoire and at the same time results in protection from disease. These studies are the first in clearly elucidating the fate of myelin basic protein-specific encephalitogenic T cells in vivo following regulation.