The FcRγ subunit and Syk kinase replace the CD3ζ-chain and ZAP-70 kinase in the TCR signaling complex of human effector CD4 T cells
The FcRγ subunit and Syk kinase replace the CD3ζ-chain and ZAP-70 kinase in the TCR signaling complex of human effector CD4 T cells
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DOI：
10.4049/jimmunol.170.8.4189
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发表时间：
2003-04-15
影响因子：
4.4
通讯作者：
Farber, DL
中科院分区：
文献类型：
--
作者：
Krishnan, S;Warke, VG;Farber, DL
活化静息T细胞所需的TCR介导的信号已得到很好的表征;然而，尚不清楚TCR偶联信号如何在协调持续免疫应答的分化效应T细胞中转导。在这里，我们证明，人效应CD 4 T细胞上调表达的CD 3 zeta相关的FcR γ信号亚基，成为一个改变的TCR/CD 3信号复合物的一部分，含有CD 3 is的一个元素，但不是CDzeta 3。效应细胞中的TCR/CD 3/FcR γ复合物募集并激活Syk酪氨酸激酶，但不激活ZAP-70酪氨酸激酶。TCR信号传导中的这种生理转换仅发生在效应T细胞中，而不是幼稚T细胞或记忆T细胞中，这表明在自身免疫性疾病、恶性疾病和感染性疾病中操纵效应反应的潜在靶点。
The TCR-mediated signals required to activate resting T cells have been well characterized; however, it is not known how TCR-coupled signals are transduced in differentiated effector T cells that coordinate ongoing immune responses. Here we demonstrate that human effector CD4 T cells up-regulate the expression of the CD3zeta-related FcRgamma signaling subunit that becomes part of an altered TCR/CD3 signaling complex containing CD3is an element of, but not CDzeta3. The TCR/CD3/FcRgamma complex in effector cells recruits and activates the Syk, but not the ZAP-70, tyrosine kinase. This physiologic switch in TCR signaling occurs exclusively in effector, and not naive or memory T cells, suggesting a potential target for manipulation of effector responses in autoimmune, malignant, and infectious diseases.