The role of CD95 in the regulation of peripheral T-cell apoptosis

Apoptosis of activated peripheral T cells during the termination phase of an immune response is critical to maintain T-cell homeostasis. Activated T cells can be removed by two mechanisms: activation-induced cell death (AICD) and death by neglect. AICD is triggered by death receptors, whereas death by neglect is induced by cytokine withdrawal. CD95 (APO-1/Fas) belongs to the subfamily of death receptors and plays a major role in AICD. In this review, we focus on the molecular mechanisms of AICD, in particular those involving the CD95 system. Moreover, we discuss the relative contribution of AICD and death by neglect to terminate a T-cell immune response. In order to become fully activated, T cells require a second signal provided by antigen-presenting cells. We discuss how these costimulatory signals counteract pro-apoptotic signals and, finally, which signals might protect T cells from death to generate a pool of memory T cells.