Podack E R
Department of Microbiology and Immunology, University of Miami School of Medicine, Florida 31101, USA.
Curr Opin Immunol. 1995 Feb;7(1):11-6. doi: 10.1016/0952-7915(95)80023-9.
With the ability to analyze cytotoxicity in animals deficient in effector molecules, the debate over the biological significance of individual effector pathways is finally being settled. For CD8+ cytotoxic T lymphocytes, the two primary cytotoxic pathways are mediated by the Fas ligand and perforin. The dichotomy between the two killing pathways is mirrored in the dichotomy between their biological roles: the primary function of the Fas ligand is the control of normal cell renewal by inducing programmed cell death of actively proliferating cells via the Fas pathway. This type of cell death is part of the normal endogenous homeostatic mechanism responsible for maintaining rapidly changing cell populations such as clonally expanding and contracting T cells. In contrast, the biological function of perforin and associated granule proteins is the killing and elimination of parasitized, non-compliant cells that arise as part of pathophysiological processes and may resist lysis pathways signalled to induce apoptosis. Thus, the main function of perforin and granzymes is the maintenance of immune surveillance against both exogenous and endogenous hazards.
凭借在缺乏效应分子的动物中分析细胞毒性的能力，关于各个效应途径生物学意义的争论终于尘埃落定。对于CD8+细胞毒性T淋巴细胞，两条主要的细胞毒性途径由Fas配体和穿孔素介导。这两条杀伤途径之间的二分法反映在它们生物学作用的二分法中：Fas配体的主要功能是通过Fas途径诱导活跃增殖细胞的程序性细胞死亡来控制正常细胞更新。这种类型的细胞死亡是正常内源性稳态机制的一部分，负责维持快速变化的细胞群体，如克隆性扩增和收缩的T细胞。相比之下，穿孔素和相关颗粒蛋白的生物学功能是杀伤和清除作为病理生理过程一部分出现的、可能抵抗诱导凋亡信号的裂解途径的寄生、不顺应细胞。因此，穿孔素和颗粒酶的主要功能是维持对外源和内源危害的免疫监视。
