Cutting edge:: Itk-dependent signals required for CD4+ T cells to exert, but not gain, Th2 effector function
Cutting edge:: Itk-dependent signals required for CD4+ T cells to exert, but not gain, Th2 effector function
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DOI：
10.4049/jimmunol.176.7.3895
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发表时间：
2006-04-01
影响因子：
4.4
通讯作者：
Fowell, Deborah J.
中科院分区：
文献类型：
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作者：
Au-Yeung, Byron B.;Katzman, Shoshana D.;Fowell, Deborah J.
对于释放 CD4 效应器功能的 TCR 信号知之甚少。 Itk 在 Th2 反应中发挥重要作用，但在 Th1 反应中则不然。然而，Th2 发育过程中何时需要 Itk 尚不清楚。我们使用 IL-41GFP 报告基因在体外和体内跟踪了 Itk 缺陷 T 细胞在 Th2 发育过程中的命运。令人惊讶的是，itk(-/-) CD4(+) 细胞分化并定型为 Th2 谱系的频率与野生型细胞相似。然而，Itk 缺陷的 Th2 细胞无法在 TCR 触发时发挥效应功能。功能丧失的标志是 Th2 细胞因子和 GATA3 的转录增强缺陷。 itk(-/-) Th2 中 IL-4 的产生可以通过激酶活性 Itk 的表达来挽救。因此，Itk 对于 Th2 功能的释放是必要的，但不是获得。我们认为效应子功能的释放是通过 TCR 信号的质变严格控制的，从而促进细胞因子反应的分化后调节。
The TCR signals for the release of CD4 effector function are poorly understood. Itk plays an essential role in Th2, but not Th1, responses. However, when Itk is required during Th2 development is unclear. We followed the fate of Itk-deficient T cells during Th2 development in vitro and in vivo using an IL-41GFP reporter. Surprisingly similar frequency of itk(-/-) CD4(+) cells differentiated and committed to the Th2 lineage as wild-type cells. However, Itk-deficient Th2 cells failed to exert effector function upon TCR triggering. Loss of function was marked by defective transcriptional enhancement of Th2 cytokines and GATA3. IL-4 production in itk(-/-) Th2s could be rescued by the expression of kinase-active Itk. Thus, Itk is necessary for the release, but not gain, of Th2 function. We suggest that the liberation of effector function is tightly controlled through qualitative changes in TCR signals, facilitating postdifferentiation regulation of cytokine responses.