CYTOLYTIC T-CELL CYTOTOXICITY IS MEDIATED THROUGH PERFORIN AND FAS LYTIC PATHWAYS
CYTOLYTIC T-CELL CYTOTOXICITY IS MEDIATED THROUGH PERFORIN AND FAS LYTIC PATHWAYS
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DOI：
10.1038/370650a0
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发表时间：
1994-08-25
期刊：
影响因子：
64.8
通讯作者：
TSCHOPP, J
中科院分区：
文献类型：
--
作者：
LOWIN, B;HAHNE, M;TSCHOPP, J
最近一代的穿孔素敲除小鼠（1，2）已经证明了孔形成穿孔素在细胞溶解性T淋巴细胞（CTL）介导的细胞溶解中的关键作用。穿孔素缺陷小鼠未能在体内清除淋巴细胞性脉络膜脑膜炎病毒，但体外无穿孔素的CTL中仍然保留了大量的杀伤活性，表明存在进一步的裂解途径。Fas是许多不同细胞表面上的凋亡信号受体分子。在这里，我们报告，穿孔素缺陷型和Fas配体缺陷型CTL对所有测试的靶细胞都显示出受损的裂解活性，当使用来自Fas受体缺陷型lpr小鼠的靶细胞和无穿孔素的CTL效应细胞灭活这两种途径时，杀伤活性完全消除。基于Fas配体的杀伤活性在T细胞受体占据后被触发，并被导向同源靶细胞。因此，两种互补的特异性细胞毒性机制在CTL中起作用，一种基于裂解蛋白的分泌，另一种依赖于细胞-表面配体-受体相互作用。
THE recent generation of perforin knock-out mice(1,2) has demonstrated a crucial role for the pore-forming perforin in cytolytic T-lymphocyte (CTL)-mediated cytolysis. Perforin-deficient mice failed to clear lymphocytic choriomeningitis virus in vivo, yet substantial killing activity still remained in perforin-free CTLs in vitro, indicating the presence of (a) further lytic pathway(s). Fas is an apoptosis-signalling receptor molecule on the surface of a number of different cells. Here we report that both perforin-deficient and Fas-ligand-deficient CTLs show impaired lytic activity on all target cells tested, The killing activity was completely abolished when both pathways were inactivated by using target cells from Fas-receptor-deficient lpr mice and perforin-free CTL effector cells. Fas-ligand-based killing activity was triggered upon T-cell receptor occupancy and was directed to the cognate target cell. Thus, two complementary, specific cytotoxic mechanisms are functional in CTLs, one based on the secretion of lytic proteins and one which depends on cell-surface ligand-receptor interaction.