GATA3 controls the expression of CD5 and the T cell receptor during CD4 T cell lineage development
GATA3 controls the expression of CD5 and the T cell receptor during CD4 T cell lineage development
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DOI：
10.1002/eji.200636485
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发表时间：
2007-04-01
影响因子：
5.4
通讯作者：
Hendriks, Rudolf W.
中科院分区：
文献类型：
--
作者：
Ling, Kam-Wing;van Hamburg, Jan Piet;Hendriks, Rudolf W.
转录因子 GATA3 在 T 细胞发育的多个阶段都是必需的，包括最早的双阴性阶段、β 选择和 CD4 单阳性胸腺细胞。在这里，我们发现在 CD2-GATA3 转基因小鼠中，在 CD2 启动子驱动下强制表达 GATA3，胸腺细胞的 CD5 水平降低，CD5 是参与 TCR 指令微调的 TCR 信号传导的负调节因子。 CD5表达的减少在CD4(+)CD8(+)双阳性(DP)细胞中最为显着，并且与转录因子E2A水平的增加相关。相反，GATA3 缺陷的 DP 胸腺细胞在向 CD4(lo)CD8(lo) 亚群发育过程中始终表现出较高的 CD5 水平和有缺陷的 TCR 上调。携带MHC II类限制性TCR DO11.10的CD2-GATA3转基因小鼠也表现出CD5水平降低。由于在这些 TCR 转基因小鼠中 CD5 表达减少并不是由 GATA3 对库选择的影响造成的，因此我们得出结论，强制 GATA3 干扰了发育调节的 CD5 水平的增加。 DO11.10 转基因小鼠中 GATA3 的强制表达还伴随着 CD4 阳性选择过程中 TCR 表达的增强。由于 GATA3 是由 DP 胸腺细胞中的 TCR 信号传导诱导的，因此我们的研究结果表明，GATA3 建立了一个正反馈环，可增加发育中的 CD4 谱系细胞中的 TCR 表面表达。
The transcription factor GATA3 is essential at multiple stages of T cell development, including the earliest double-negative stages, beta-selection and CD4 single-positive thymocytes. Here, we show that in CD2-GATA3 transgenic mice, with enforced GATA3 expression driven by the CD2 promoter, thymocytes have reduced levels of CD5, which is a negative regulator of TCR signaling participating in TCR repertoire fine-tuning. Reduction of CD5 expression was most prominent in CD4(+)CD8(+) double-positive (DP) cells and was associated with increased levels of the transcription factor E2A. Conversely, GATA3-deficient DP thymocytes showed consistently higher CD5 levels and defective TCR up-regulation during their development towards the CD4(lo)CD8(lo) subpopulation. CD2-GATA3 transgenic mice carrying the MHC class II-restricted TCR DO11.10 also manifested decreased CD5 levels. As in these TCR-transgenic mice reduced CD5 expression cannot result from an effect of GATA3 on repertoire selection, we conclude that enforced GATA3 interferes with the developmentally regulated increase of CD5 levels. Enforced GATA3 expression in DO11.10 transgenic mice was also accompanied by enhanced TCR expression during CD4 positive selection. Because GATA3 is induced by TCR signaling in DP thymocytes, our findings indicate that GATA3 establishes a positive feedback loop that increases TCR surface expression in developing CD4 lineage cells.