Differential requirements for ZAP-70 in TCR signaling and T cell development.
Differential requirements for ZAP-70 in TCR signaling and T cell development.
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DOI：
10.4049/jimmunol.161.9.4688
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发表时间：
1998-11
影响因子：
4.4
通讯作者：
T. Kadlecek;N. S. C. V. Oers;Leo Lefrançois;S. Olson;D. Finlay;D. Chu;K. Connolly;Nigel Killeen;Arthur Weiss
中科院分区：
文献类型：
--
作者：
T. Kadlecek;N. S. C. V. Oers;Leo Lefrançois;S. Olson;D. Finlay;D. Chu;K. Connolly;Nigel Killeen;Arthur Weiss
Syk/ZAP-70 蛋白酪氨酸激酶家族对于正常淋巴发育是不可或缺的。 Syk 对于 B 细胞和上皮 γδ T 细胞的发育是必需的，而 ZAP-70 对于 T 细胞和 TCR 信号传导的正常发育是必需的。在这项研究中，我们发现，虽然胸腺中 Alphata 谱系的发育受到抑制，但缺乏 ZAP-70 的小鼠的淋巴结中存在 CD3 阳性 T 细胞（主要是 γδ 谱系）。此外，在缺乏ZAP-70的情况下，树突状表皮T细胞数量较少且形态异常，通常含有大量γδT细胞的肠上皮内淋巴细胞显着减少。这些数据表明，gammadelta T 细胞的发育对 ZAP-70 表现出可变的依赖性。胸腺细胞的生化分析显示缺乏基础 zeta 链酪氨酸磷酸化。然而，其他几种底物在 TCR 刺激后被诱导酪氨酸磷酸化。因此，ZAP-70 缺陷型胸腺细胞中 TCR 介导的信号传导仅部分受损。这些研究表明，Syk 仅部分补偿了 ZAP-70 的损失，并且 Alphata T 细胞和上皮 γδ T 细胞需要 ZAP-70，但外周淋巴组织中的某些 γδ T 细胞则不需要 ZAP-70。
The Syk/ZAP-70 family of protein tyrosine kinases is indispensable for normal lymphoid development. Syk is necessary for the development of B cells and epithelial gammadelta T cells, whereas ZAP-70 is essential for the normal development of T cells and TCR signaling. In this study, we show that although development of the alphabeta lineage was arrested in the thymus, CD3-positive T cells, primarily of the gammadelta lineage, were present in the lymph nodes of mice lacking ZAP-70. Moreover, in the absence of ZAP-70, dendritic epidermal T cells were fewer in number and of abnormal morphology, and intestinal intraepithelial lymphocytes, normally containing a large proportion of gammadelta T cells, were markedly reduced. These data suggest that gammadelta T cells show a variable dependence upon ZAP-70 for their development. Biochemical analyses of thymocytes revealed a lack of basal zeta-chain tyrosine phosphorylation. However, several other substrates were inducibly tyrosine phosphorylated following TCR stimulation. Thus, TCR-mediated signaling in ZAP-70-deficient thymocytes is only partially impaired. These studies suggest that Syk compensates only partially for the loss of ZAP-70, and that there is an absolute requirement of ZAP-70 for alphabeta T cells and epithelial gammadelta T cells, but not for some gammadelta T cells in peripheral lymphoid tissues.