Berke G
Department of Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Immunol Rev. 1995 Aug;146:21-31. doi: 10.1111/j.1600-065x.1995.tb00681.x.
The central role of CTLs in immunopathology accounts for the increasing interest in deciphering the mechanism whereby they kill at the molecular level. Recent studies show that CTLs have two molecularly distinct lytic mechanisms at their disposal. The first involves the direct effect(s) of the pore-forming protein perforin, possibly in conjunction with granzymes. In recent years, experiments conducted in our laboratory led to an alternative pathway, of receptor-mediated mechanism for CTL killing, involving neither the secretion nor the lytic action of the pore-forming protein perforin or of granzymes. By this mechanism, engagement of a CTL membrane ligand and an apoptosis-inducing target cell surface receptor triggers the disintegration of the CTL-bound target cell. Cross-linking of apoptosis-inducing target cell surface molecules (e.g. Fas), induced upon binding of CTL ligands (e.g. Fas-L), may be required and sufficient to trigger target cell apoptosis. Intracellular lethal signals emanating from the cross-linked intracellular death domain of Fas are postulated.
细胞毒性T淋巴细胞（CTLs）在免疫病理学中的核心作用使得人们越来越有兴趣去破译它们在分子水平上的杀伤机制。最近的研究表明，CTLs有两种分子上截然不同的裂解机制可供使用。第一种涉及成孔蛋白穿孔素的直接作用，可能与颗粒酶协同作用。近年来，我们实验室进行的实验导致了另一种途径，即CTL杀伤的受体介导机制，该机制既不涉及成孔蛋白穿孔素或颗粒酶的分泌，也不涉及它们的裂解作用。通过这种机制，CTL膜配体与凋亡诱导靶细胞表面受体的结合会触发与CTL结合的靶细胞解体。CTL配体（如Fas-L）结合后诱导的凋亡诱导靶细胞表面分子（如Fas）的交联可能是触发靶细胞凋亡所必需且足够的。据推测，Fas交联的细胞内死亡结构域会发出细胞内致死信号。
