Role of apoptosis in the immune system.

Abstract

Apoptosis is becoming recognized as a fundamental component of the immune system, i.e., in its development and its regulation. It is involved in many diverse areas that fall into two broad categories: firstly, the development and shaping of the immune receptor repertoire and, secondly, immune effector mechanisms. We have employed several model systems for analysing the development of the immune system, e.g., haemopoietic progenitor cell development and thymocyte development and selection, as well as the role of apoptosis in CD4+ T-cell-mediated cytotoxicity. These studies have helped illustrate the fundamental role of active cell death in the physiological functioning of the immune system. Failure of such a fundamental process would be expected to have serious consequences and we have been particularly involved in analysing the role of inappropriate suppression of apoptosis by the BCL2 family of genes both in oncogenesis in the immune system and in the development of cancer cell resistance to therapy. It seems likely that this is only one of many mechanisms by which apoptosis may be disrupted with pathological consequences.