ROLE OF APOPTOSIS IN THE IMMUNE-SYSTEM

Apoptosis is becoming recognized as a fundamental component of the imm une system, i.e., in its development and its regulation. It is involve d in many diverse areas that fall into two broad categories: firstly, the development and shaping of the immune receptor repertoire and, sec ondly, immune effector mechanisms. We have employed several model syst ems for analysing the development of the immune system, e.g., haemopoi etic progenitor cell development and thymocyte development and selecti on, as well as the role of apoptosis in CD4(+) T-cell-mediated cytotox icity. These studies have helped illustrate the fundamental role of ac tive cell death in the physiological functioning of the immune system. Failure of such a fundamental process would be expected to have serio us consequences and we have been particularly involved in analysing th e 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 on ly one of many mechanisms by which apoptosis may be disrupted with pat hological consequences.