Resting dendritic cells induce peripheral CD8+ T cell tolerance through PD-1 and CTLA-4
Resting dendritic cells induce peripheral CD8+ T cell tolerance through PD-1 and CTLA-4
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DOI：
10.1038/ni1165
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发表时间：
2005-03-01
影响因子：
30.5
通讯作者：
van den Broek, M
中科院分区：
文献类型：
--
作者：
Probst, HC;McCoy, K;van den Broek, M
识别自身蛋白质的T细胞存在于健康个体中而不引起自身免疫。这些自身反应性T细胞被外周耐受性控制。使用由体内静息树突状细胞的抗原呈递引起的外周CD 8（+）T细胞耐受模型，我们在这里表明，CD 8（+）T细胞耐受通过T细胞内在机制如缺失或功能失活而起作用。外周CD 8（+）T细胞耐受依赖于通过共刺激分子PD-1的信号传导，因为缺乏PD-1将耐受诱导转化为引发。共刺激分子CTLA-4的阻断导致耐受性受损，并增强了PD-1缺失的效果，表明PD-1和CTLA-4协同作用。因此，PD-1和CTLA-4是由静息树突状细胞诱导的外周CD 8（+）T细胞耐受的关键分子。
T cells recognizing self proteins exist without causing autoimmunity in healthy individuals. These autoreactive T cells are kept in check by peripheral tolerance. Using a model for peripheral CD8(+) T cell tolerance resulting from antigen presentation by resting dendritic cells in vivo, we show here that CD8(+) T cell tolerance operates through T cell-intrinsic mechanisms such as deletion or functional inactivation. Peripheral CD8(+) T cell tolerance depended on signaling via the costimulatory molecule PD-1, as an absence of PD-1 converted tolerance induction into priming. Blocking of the costimulatory molecule CTLA-4 resulted in impaired tolerance and enhanced the effect of the absence of PD-1, suggesting that PD-1 and CTLA-4 act synergistically. Thus PD-1 and CTLA-4 are crucial molecules for peripheral CD8(+) T cell tolerance induced by resting dendritic cells.