Activation-induced apoptosis in lymphoid systems

Lymphocytes become activated when antigen receptors on the cell surface are cross-linked, or when they are exposed to agents that mimic this signal. Although such activation is usually associated with the production of immune mediators (e.g. antibodies, cytokines) and entry into the cell cycle, it can alternatively lead to death via apoptosis. This activation-induced apoptosis was first observed in developing lymphocytes and has been proposed as a mechanism for negative selection, by which immature cells with potential for autoreactivity are eliminated from the maturation pathway. Activation-induced apoptosis has also been observed in normal, mature lymphocytes under some conditions, and this may account for the phenomena of peripheral deletion, in which mature T cells are eliminated upon exposure to high doses of antigen. It may also be an important mechanism whereby CD4+ T cells are depleted in HIV+ individuals. Although the phenomenon of activation-induced apoptosis is not understood, recent studies have begun to implicate specific signal transduction pathways and gene products in the process. Among the latter is the c-myc proto-oncogene, which paradoxically can play an essential role in several forms of apoptosis, including that induced by activation of lymphocytes.