Programming for cytotoxic effector function occurs concomitantly with CD4 extinction during CD8(+) T cell differentiation in the thymus.
Programming for cytotoxic effector function occurs concomitantly with CD4 extinction during CD8(+) T cell differentiation in the thymus.
复制标题
细胞毒效应功能的编程与胸腺中 CD8(+) T 细胞分化期间的 CD4 消亡同时发生。
DOI：
10.1093/intimm/12.7.1035
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发表时间：
2000
影响因子：
4.4
通讯作者：
Singer,A
中科院分区：
文献类型：
--
作者：
Bhandoola,A;Kithiganahalli,B;Granger,L;Singer,A
CD4+T细胞通常专门用作辅助细胞，CD8+T细胞通常专门用作细胞毒性效应细胞。为了解释辅助受体表达和免疫功能之间如何实现这种一致性，我们考虑了两种可能性。在一种情况下，未成熟的CD4+CD8+胸腺细胞前体可能首先下调一种辅助受体分子的表达，而剩余的辅助受体分子随后激活适当的辅助或细胞毒性功能程序。或者，我们认为选择性消除一种或另一种共受体分子表达的相同胸腺内信号可能同时启动适当的辅助或细胞毒性功能程序。在本研究中，我们试图通过检查 CD8+T 细胞的胸腺细胞前体组织蛋白酶 C 和组织蛋白酶 W 的表达来区分这些替代方案，这两种分子对细胞毒效应功能很重要。我们报道，在发育中的胸腺细胞中，组织蛋白酶 C 和组织蛋白酶 W 的表达与 CD4 辅助受体表达的消失相协调。我们得出结论，在胸腺中 CD8+T 细胞分化过程中，CD4 消亡和细胞毒性功能程序的启动同时发生。
CD4+T cells are generally specialized to function as helper cells and CD8+T cells are generally specialized to function as cytotoxic effector cells. To explain how such concordance is achieved between co-receptor expression and immune function, we considered two possibilities. In one case, immature CD4+CD8+thymocyte precursors might first down-regulate expression of one co-receptor molecule, with the remaining co-receptor molecule subsequently activating the appropriate helper or cytotoxic functional program. Alternatively, we considered that the same intrathymic signals that selectively extinguished expression of one or the other co-receptor molecule might simultaneously initiate the appropriate helper or cytotoxic functional program. In the present study, we attempted to distinguish between these alternatives by examining thymocyte precursors of CD8+T cells for expression of Cathepsin C and Cathepsin W, molecules important for cytotoxic effector function. We report in developing thymocytes that Cathepsin C and Cathepsin W are expressed coordinately with extinction of CD4 co-receptor expression. We conclude that CD4 extinction and initiation of the cytotoxic functional program occurs simultaneously during differentiation of CD8+T cells in the thymus.