Mechanisms of Lymphocyte Activation and Immune Regulation VI

Shigekazu Nagata, Nagata, Shigekazu

Homeostasis in vertebrates is tightly regulated by cell death as well as by cell proliferation. The death of cells during embryogenesis, metamorphosis, endocrine-dependent tissue atrophy, and normal tissue turnover is "programmed cell death", mediated by a process called "apoptosis". Cytotoxic T lymphocytes and natural killer cells kill the target cells by inducing apoptosis. Apoptosis can be distinguished from necrosis, which occurs as a result of injury, complement attack, severe hypoxia and hyperthermia. Morphological and biochemical analyses of the apoptotic cell death process indicated that apoptosis is accompanied by condensation of cytoplasm, loss of plasma membrane microvilli, segmentation of nucleus, and extensive degradation of chromosomal DNA into oligomers of 180 bp. Cellular proliferation and differentiation are mediated by a family of proteins called cytokines. Our studies on the Fas ligand and Fas have indicated that apoptosis is also mediated by a cytokine and its receptor in some cases. Here, I summarize the current status of the Fas death factor system.