ROLE OF APOPTOSIS IN THE REGULATION OF VIRUS-INDUCED T-CELL RESPONSES, IMMUNE SUPPRESSION, AND MEMORY

Apoptosis is an important mechanism enabling the selection of the non- self-reactive T cell repertoire and for maintaining homeostasis in the immune system after it has expanded to combat infections. Highly acti vated, proliferating T cells become susceptible to apoptosis driven by a number of stimuli, and T cells activated during a viral infection b ecome susceptible to ''activation induced cell death'' after repeated stimulation through the T cell receptor (TcR). This is a major mechani sm for the immune deficiencies observed during many viral infections. During infections with a high antigen load this can lead to a selectiv e deletion of virus-specific cytotoxic T lymphocytes (CTL) and to the establishment of persistent infection. More commonly, the CTL control the infection first, and high levels of apoptosis in the expanded lymp hocyte population occur after antigen and growth factors become limiti ng. This cell death does not seem to depend on TcR specificity, as the residual population contains a remarkably stable population of memory CTL precursors that approximate the frequency per CD8 cell of that se en during the peak of the acute infection. Subsequent infections with heterologous viruses result in an expansion and then an apoptotic elim ination of T cells, with the consequence being a reduction in precurso r CTL specific for the first virus. Thus, apoptosis shapes the quality and quantity of T cell memory. (C) 1995 Wiley-Liss, Inc.