RESISTANCE OF CYTOLYTIC LYMPHOCYTES TO PERFORIN-MEDIATED KILLING - LACK OF CORRELATION WITH COMPLEMENT-ASSOCIATED HOMOLOGOUS SPECIES RESTRICTION
RESISTANCE OF CYTOLYTIC LYMPHOCYTES TO PERFORIN-MEDIATED KILLING - LACK OF CORRELATION WITH COMPLEMENT-ASSOCIATED HOMOLOGOUS SPECIES RESTRICTION
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DOI：
10.1084/jem.168.6.2207
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发表时间：
1988-12-01
影响因子：
15.3
通讯作者：
YOUNG, JDE
中科院分区：
文献类型：
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作者：
JIANG, S;PERSECHINI, PM;YOUNG, JDE
CTL和NK细胞通过其自身的孔形成蛋白（PFP;穿孔素）抵抗自身介导的杀伤和裂解。穿孔素，像C一样，溶解RBC。当C和RBC来自不同物种时，发生有效的C介导的RBC裂解（同源物种限制）。据报道，保护性表面蛋白（C8结合蛋白，同源限制因子）介导C依赖性细胞溶解中的同源物种限制和保护某些靶细胞免受穿孔素诱导的溶解。我们在这里表明，穿孔素，不像C，裂解各种物种的靶细胞，包括同源的，而相同的靶细胞群体抵抗同源C的攻击。针对来自10个不同物种的RBC、几种有核靶细胞系和一种原代细胞群（胸腺细胞），测试了来自三个物种（大鼠、小鼠和人）的CTL和LAK/NK细胞的含穿孔素提取物和纯化的小鼠穿孔素。在抵抗同源C裂解的同时，这些细胞类型中的大多数被穿孔素有效地裂解，而没有任何同源限制性模式。CTL和NK细胞与其他有核靶细胞一样，对同源而非异源C的裂解具有抗性;然而，这些细胞类型对同源和异源穿孔素都具有抗性。总之，我们的研究结果表明，与C-和穿孔素介导的溶解的保护机制是不同的。
CTL and NK cells resist self-mediated killing and lysis by their own pore-forming protein (PFP; perforin). Perforin, like C, lyses RBC. Efficient C-mediated lysis of RBC occurs when both C and RBC are from different species (homologous species restriction). A protective surface protein (C8-binding protein, homologous restriction factor) has been reported to mediate both homologous species restriction in C-dependent cytolysis and protection of some target cells against perforin-induced lysis. We show here that perforin, unlike C, lyses target cells across a variety of species, including the homologous one, while the same target cell populations resist the attack by homologous C. Perforin-containing extracts of CTL and LAK/NK cells from three species (rat, mouse, and human) and purified mouse perforin were tested against RBC from 10 different species, several nucleated target cell lines, and one primary cell population (thymocytes). While resisting lysis by homologous C, most of these cell types were lysed effectively by perforin without any homologous restriction pattern. CTL and NK cells, like other nucleated targets, are resistant to lysis by homologous but not heterologous C; however, these cell types are resistant to both homologous and heterologous perforin. Together, our results suggest that the protective mechanisms associated with C- and perforin-mediated lysis are distinct.