Biochemical mechanisms of IL-2-regulated Fas-mediated T cell apoptosis
Biochemical mechanisms of IL-2-regulated Fas-mediated T cell apoptosis
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DOI：
10.1016/s1074-7613(00)80566-x
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发表时间：
1998-05-01
期刊：
影响因子：
32.4
通讯作者：
Abbas, AK
中科院分区：
文献类型：
--
作者：
Refaeli, Y;Van Parijs, L;Abbas, AK
激活诱导淋巴细胞死亡（AICD）是一种重要的自我耐受机制。在CD4(+) T细胞中，AICD由Fas途径介导，并由IL-2增强。为了确定IL-2促凋亡作用的机制，我们分析了表达转基因T细胞受体的野生型和IL-2（-/-）小鼠的CD4(+) T细胞。T细胞在被抗原和IL-2激活后对AICD敏感。IL-2增加Fas配体（FasL）的转录和表面表达，抑制凋亡抑制剂FLIP的转录和表达。IL-2增强促凋亡分子Fast的表达和抑制Fas信号抑制剂FLIP的能力可能解释了这种细胞因子在促进T细胞凋亡中的作用。
Activation-induced cell death (AICD) of lymphocytes is an important mechamism of self-tolerance. In CD4(+) T cells, AICD is mediated by the Fas pathway and is enhanced by IL-2. To define the mechanisms of this pro-apoptotic action of IL-2, we analyzed CD4(+) T cells from wild-type and IL-2(-/-) mice expressing a transgenic T cell receptor. T cells become sensitive to AICD after activation by antigen and IL-2. IL-2 increases transcription and surface expression of Fas ligand (FasL) and suppresses transcription and expression of FLIP, the inhibitor of apoptosis. The ability of IL-2 to enhance expression of a pro-apoptotic molecule, Fast, and to suppress an inhibitor of Fas signaling, FLIP, likely accounts for the role of this cytokine in potentiating T cell apoptosis.