BCL-X-L-regulated apoptosis in T cell development
BCL-X-L-regulated apoptosis in T cell development
复制标题
DOI：
10.1093/intimm/9.9.1375
复制
发表时间：
1997-09-01
影响因子：
4.4
通讯作者：
Korsmeyer, SJ
中科院分区：
文献类型：
--
作者：
Chao, DT;Korsmeyer, SJ
在胸腺细胞分化过程中，凋亡是选择功能性TCR库的核心。在本研究中，我们探讨了凋亡抑制因子BCL-X-L对发育的影响。我们发现内源性BCL-X-L在胸腺细胞发育的CD4(+) CD8（+）阶段受到阳性和阴性选择信号的下调，我们在α - β TCR转基因、rag1缺失和scid模型的背景下研究了BCL-X-L可调节的凋亡在T细胞发育中的作用，我们发现即使在MHC ii类限制性TCR转基因小鼠中，BCL-X-L的表达也促进了CD8单阳性胸腺细胞的积累。BCL-X-L赋予的凋亡抗性不能完全替代tcr介导的正选择信号，也不能阻止负选择信号。在ragg缺乏的背景下，BCL-X-L的过度表达促进了CD4(-)CD8（-）胸腺细胞向CD4(+)CD8（+）胸腺细胞的部分成熟。因此，tcr介导的信号介导了胸腺细胞发育过程中内源性BCL-X-L的调节，表明BCL-X-L对双阳性胸腺细胞的主要保护发生在选择之前。BCL-X-L对CD8而不是CD4谱系的影响支持了谱系承诺的不对称模型。T细胞发育的几个关键控制点可以区分为BCL-X-L反应性或无反应性。
Thymocyte differentiation progresses through well-defined stages in which apoptosis is central to the selection of a functional TCR repertoire, In the present study, we explored the developmental effects of BCL-X-L, a repressor of apoptosis. We found that endogenous BCL-X-L is down-regulated by both positive and negative selection signals at the CD4(+) CD8(+) stage of thymocyte development, We examined the role of BCL-X-L regulatable apoptosis in T cell development in the context of an alpha beta TCR transgene, Rag-1 deficiency and the scid model, We found that BCL-X-L expression promoted accumulation of CD8 single-positive thymocytes even in MHC class Ii-restricted TCR transgenic mice, However, the apoptotic resistance conferred by BCL-X-L could not fully substitute for TCR-mediated positive selection signals nor did it prevent negative selection. Overexpression of BCL-X-L promoted partial maturation of CD4(-)CD8(-) thymocytes to CD4(+)CD8(+) cells in a Rag-deficient, but not a scid background, Thus, TCR-mediated signals mediate the regulation of endogenous BCL-X-L during thymocyte development, indicating that the principal protection of double-positive thymocytes by BCL-X-L occurs prior to selection, The impact of BCL-X-L on the CD8 but not CD4 lineage supports the asymmetric model of lineage commitment, Moreover, several critical control points in T cell development could be distinguished as BCL-X-L responsive or unresponsive.