Regulation of activation-induced cell death of mature T-lymphocyte populations

Resting mature T lymphocytes are activated when triggered via their antigen -specific T-cell receptor (TCR) to elicit an appropriate immune response. I n contrast, preactivated T cells may undergo activation-induced cell death (AICD) in response to the same signals. Along with cell death induced by gr owth factor deprivation, AICD followed by the elimination of useless or pot entially harmful cells preserves homeostasis, leads to the termination of c ellular immune responses and ensures peripheral tolerance. T-cell apoptosis and AICD are controlled by survival cytokines such as interleukin-2 (IL-2) and by death factors such as tumor necrosis factor (TNF) and CD95 ligand ( CD95L). In AICD-sensitive T cells, stimulation upregulates expression of on e or several death factors, which in turn engage specific death receptors o n the same or a neighboring cell. Death receptors are activated by oligomer ization to rapidly assemble a number of adapter proteins and enzymes to res ult in an irreversible activation of proteases and nucleases that culminate s in cell death by apoptosis. Increased knowledge of the molecular mechanis ms that regulate AICD of lymphocytes opens new immunotherapeutic perspectiv es for the treatment of certain autoimmune diseases, and has implications i n other areas such as transplantation medicine and AIDS research.