Dual function of CTLA-4 in regulatory T cells and conventional T cells to prevent multiorgan autoimmunity
Dual function of CTLA-4 in regulatory T cells and conventional T cells to prevent multiorgan autoimmunity
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DOI：
10.1073/pnas.0910341107
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发表时间：
2010-01-26
影响因子：
11.1
通讯作者：
Kang, Joonsoo
中科院分区：
文献类型：
--
作者：
Jain, Nitya;Nguyen, Hai;Kang, Joonsoo
细胞毒性T淋巴细胞抗原-4（CTLA-4）是T细胞上的抑制性受体，对维持T细胞稳态和对自身的耐受至关重要。缺乏CTLA-4的小鼠在T细胞耐受性中发展出早期发作的致命性破坏。这种自身免疫性疾病的发生是否是因为调节性T细胞、常规T细胞或两者中CTLA-4功能的丧失尚不清楚。我们在这里表明，缺乏CTLA-4的调节性T细胞导致异常激活和常规T细胞的扩增。然而，常规T细胞中的CTLA-4表达防止异常活化的T细胞浸润和致命地损伤非淋巴组织。这些结果表明，CTLA-4在维持T细胞耐受性方面具有双重功能：调节性T细胞中的CTLA-4抑制不适当的幼稚T细胞活化，而常规T细胞中的CTLA-4防止自身反应性病原性T细胞在重要器官中的有害积累。
Cytotoxic T lymphocyte antigen-4 (CTLA-4) is an inhibitory receptor on T cells essential for maintaining T cell homeostasis and tolerance to self. Mice lacking CTLA-4 develop an early onset, fatal breakdown in T cell tolerance. Whether this autoimmune disease occurs because of the loss of CTLA-4 function in regulatory T cells, conventional T cells, or both is unclear. We show here that lack of CTLA-4 in regulatory T cells leads to aberrant activation and expansion of conventional T cells. However, CTLA-4 expression in conventional T cells prevents aberrantly activated T cells from infiltrating and fatally damaging non-lymphoid tissues. These results demonstrate that CTLA-4 has a dual function in maintaining T cell tolerance: CTLA-4 in regulatory T cells inhibits inappropriate naive T cell activation and CTLA-4 in conventional T cells prevents the harmful accumulation of self-reactive pathogenic T cells in vital organs.