Cutting edge: CD95 maintains effector T cell homeostasis in chronic immune activation
Cutting edge: CD95 maintains effector T cell homeostasis in chronic immune activation
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DOI：
10.4049/jimmunol.174.10.5915
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发表时间：
2005-05-15
影响因子：
4.4
通讯作者：
van Lier, RAW
中科院分区：
文献类型：
--
作者：
Arens, R;Baars, PA;van Lier, RAW
清除激活的T细胞对维持体内平衡和避免免疫病理很重要。CD95(TaslAPO-1)已被认为是体外激活T细胞的死亡介质，但CD95在体内成熟T细胞死亡中的作用仍存在争议。在此，我们证明了共刺激的肿瘤坏死因子受体家族成员CD27可使T细胞敏化CD95诱导的凋亡。CD95缺陷(LPR/LPR)T细胞在表达CD27配体CD70的转基因小鼠中大量扩增和分化为分泌干扰素-γ的效应细胞。与此同时，CD95缺陷的CD70转基因小鼠在4周龄时死亡，并伴有严重的肝脏病理和骨髓衰竭。这些发现证实CD95在慢性免疫激活中是效应T细胞稳态的关键调节因子。
The elimination of activated T cells is important to maintain homeostasis and avoid immunopathology. CD95 (TaslAPO-1) has been identified as a death mediator for activated T cells in vitro but the function of CD95 in death of mature T cells in vivo is still controversial Here we show that triggering of the costimulatory TNF receptor family member CD27 sensitized T cells for CD95-induced apoptosis. CD95-deficient (lpr/lpr) T cells massively expanded and differentiated into IFN-gamma-secreting effector cells in transgenic mice that constitutively express the CD27 ligand, CD70. Concomitantly, CD95-deficient CD70 transgenic mice became moribund by 4 wk of age with severe liver pathology and bone marrow failure. These findings establish that CD95 is a critical regulator of effector T cell homeostasis in chronic immune activation.