King L B, Ashwell J D
Laboratory of Immune Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Thymus. 1994;23(3-4):209-30.
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.
在胸腺细胞发育过程中，潜在的自身反应性胸腺细胞通过一种称为凋亡或程序性细胞死亡的过程被清除。虽然长期以来人们都知道，这种对自身抗原有高亲和力的表达T细胞受体的胸腺细胞的克隆清除或阴性选择在维持自身耐受性方面起主要作用，但现在很明显，凋亡在维持外周T细胞耐受性方面也可能发挥积极作用。虽然很清楚凋亡在塑造免疫反应中起主要作用，但负责其诱导的机制以及影响细胞死亡易感性的调节机制尚未得到很好的表征。在本文中，我们将集中讨论该领域的一些最新发现。特别是，我们将强调以Bcl-2家族成员为例的保护性“变阻器”机制，以及Fas在激活诱导的凋亡中的作用。此外，我们将比较触发胸腺细胞和外周T细胞凋亡的生理信号，并讨论中枢和外周细胞清除是否受相似或不同机制的调节。
