Programmed Cell Death Mediated by Members of the TNF Receptor Family

Cell death can, at times, be more vital to the organism than cell life. Witness the severity of disease that is caused by a discrete failure of apoptosis (in mice homozygous for the /pr or g/d mutations), as compared with the severity of disease caused by total T-cell aplasia (in mice homozygous for the nu mutation). Arguably, lymphoproliferation is a more serious problem. There is reason to believe that many autoimmune diseases might result from similar failures of apoptosis, and concomitant sutvival of an immune response beyond its useful lifetime. The TNF receptors and their homologs act as discrete molecular switches in this process, and in understanding the signal transduction apparatus that sewes them, it is likely that much might be learned of perplexing diseases. Further, a more sophisticated approach to the induction of apoptosis might be fashioned with therapeutic intent.