Thymocyte and T cell apoptosis: is all death created equal?

Abstract

During thymocyte development, potentially autoreactive thymocytes are eliminated by a process known as apoptosis or programmed cell death. While it has long been known that this clonal elimination or negative selection of thymocytes expressing T cell receptors with high affinity for self antigens plays a major role in preserving self tolerance, it is now apparent that apoptosis may also play an active role in maintaining peripheral T cell tolerance. Although it is clear that apoptosis plays a major role in shaping the immune response, the mechanisms responsible for its induction and the regulatory mechanisms that influence susceptibility to cell death are not well characterized. In this article, we will concentrate on some of the most recent findings in this area. In particular, we will emphasize the protective 'rheostat' mechanism exemplified by the Bcl-2 family members, and the role of Fas in activation-induced apoptosis. In addition, we will compare the physiologic signals that trigger apoptosis in thymocytes and peripheral T cells, and discuss whether central and peripheral deletion are regulated by similar or distinct mechanisms.