Sentman C L, Shutter J R, Hockenbery D, Kanagawa O, Korsmeyer S J
Howard Hughes Medical Institute, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
Cell. 1991 Nov 29;67(5):879-88. doi: 10.1016/0092-8674(91)90361-2.
The vast majority of cortical thymocytes die during T cell development while those that survive this selective process accumulate in the medulla. bcl-2, an inner mitochondrial membrane protein, has been shown to inhibit apoptosis in certain cell lines. In the thymus, bcl-2 is regionally localized to the mature T cells of the medulla. To assess the role of bcl-2 in the programmed death of thymocytes, we generated transgenic mice that redirected bcl-2 expression to cortical thymocytes. bcl-2 protected immature CD4+8+ thymocytes from glucocorticoid, radiation, and anti-CD3-induced apoptosis. Moreover, bcl-2 altered T cell maturation, resulting in increased percentages of CD3hi and CD4-8+ thymocytes. Despite this, clonal deletion of T cells that recognize endogenous superantigens still occurred. This transgenic model indicates that multiple death pathways operate within the thymus that can be distinguished by their dependence on bcl-2.
绝大多数皮质胸腺细胞在T细胞发育过程中死亡，而那些在这个选择过程中存活下来的细胞则在髓质中积累。bcl-2是一种线粒体内膜蛋白，已被证明能抑制某些细胞系中的细胞凋亡。在胸腺中，bcl-2区域定位于髓质的成熟T细胞。为了评估bcl-2在胸腺细胞程序性死亡中的作用，我们构建了将bcl-2表达重定向至皮质胸腺细胞的转基因小鼠。bcl-2保护未成熟的CD4+8+胸腺细胞免受糖皮质激素、辐射和抗CD3诱导的细胞凋亡。此外，bcl-2改变了T细胞成熟，导致CD3hi和CD4-8+胸腺细胞百分比增加。尽管如此，识别内源性超抗原的T细胞的克隆性缺失仍会发生。这个转基因模型表明，胸腺内存在多种死亡途径，它们可根据对bcl-2的依赖性加以区分。
