Requirement for T-cell apoptosis in the induction of peripheral transplantation tolerance
Requirement for T-cell apoptosis in the induction of peripheral transplantation tolerance
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DOI：
10.1038/15260
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发表时间：
1999-11-01
期刊：
影响因子：
82.9
通讯作者：
Turka, LA
中科院分区：
文献类型：
--
作者：
Wells, AD;Li, XC;Turka, LA
同种异体移植耐受的机制可分为缺失、无能、忽视和抑制/调节机制。缺失与中枢耐受有关(1)，而外周耐受通常归因于克隆性无能和/或主动免疫调节状态(2)。在这里，我们使用两种不同的系统来评估外周耐受诱导中T细胞缺失的要求。在转Bclx基因的小鼠(L)中，T细胞通过细胞因子的退出抵抗被动细胞死亡，而来自白细胞介素2缺乏的小鼠的T细胞不经历激活诱导的细胞死亡。使用阻断共刺激通路的药物或免疫抑制药物雷帕霉素，我们在这里展示了阻断白细胞介素2信号的增殖成分，但不抑制激活诱导细胞死亡的启动，我们发现，被动或主动T细胞凋亡通路有缺陷的小鼠对诱导移植耐受具有抵抗力。因此，通过激活诱导的细胞死亡或生长因子撤除来删除激活的T细胞似乎对于实现跨越主要组织相容性复合体屏障的外周耐受是必要的。
The mechanisms of allograft tolerance have been classified as deletion, anergy, ignorance and suppression/regulation. Deletion has been implicated in central tolerance(1), whereas peripheral tolerance has generally been ascribed to clonal anergy and/or active immunoregulatory states(2). Here, we used two distinct systems to assess the requirement for T-cell deletion in peripheral tolerance induction. in mice transgenic for Bcl-x(L), T cells were resistant to passive cell death through cytokine withdrawal, whereas T cells from interleukin-2-deficient mice did not undergo activation-induced cell death. Using either agents that block co-stimulatory pathways or the immunosuppressive drug rapamycin, which we have shown here blocks the proliferative component of interleukin-2 signaling but does not inhibit priming for activation-induced cell death, we found that mice with defective passive or active T-cell apoptotic pathways were resistant to induction of transplantation tolerance. Thus, deletion of activated T cells through activation-induced cell death or growth factor withdrawal seems necessary to achieve peripheral tolerance across major histocompatibility complex barriers.