GATA-3 regulates the homeostasis and activation of CD8+ T cells.

GATA-3 regulates the homeostasis and activation of CD8+ T cells.
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DOI:
10.4049/jimmunol.1201361
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发表时间:
2013-01-01
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Ho IC
Ho IC
中科院分区:
其他
文献类型:
--
作者:
Tai TS;Pai SY;Ho IC

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GATA-3是一种C2C2型锌指转录因子,调控T细胞发育和分化的许多步骤。它也是CD8+ T细胞产生2型细胞因子的最佳条件。然而,其在T细胞亚群的发育和功能中的作用仍不清楚。在这里,我们报道GATA-3是mhc介导的阳性选择和CD8单阳性胸腺细胞最终成熟所必需的。由CD4cre转基因介导的GATA-3缺失导致年龄依赖性淋巴结病,部分原因是由细胞外源性机制驱动的CD8+ T细胞异常扩增。矛盾的是,gata -3缺陷的CD8+ T细胞对抗原刺激反应低下是由于激活信号的维持/进展缺陷,而不是启动缺陷。更重要的是,gata -3缺陷的CD8+ T细胞在体内杀死携带抗原的肿瘤细胞的效率较低。综上所述,我们的数据进一步扩展了GATA-3在T细胞中的作用。
GATA-3, a C2C2 type zinc finger transcription factor, regulates many steps of T cell development and differentiation. It is also required for optimal production of type 2 cytokines by CD8+ T cells. However, its role in the development and function of this subset of T cells is still poorly characterized. Here we report that GATA-3 is required for MHC-mediated positive selection and final maturation of CD8 single positive thymocytes. Deficiency of GATA-3 mediated by a CD4cre transgene led to age-dependent lymphadenopathy partly due to abnormal expansion of CD8+ T cells driven by a cell-extrinsic mechanism. Paradoxically, GATA-3-deficient CD8+ T cells were hyporesponsive to antigen stimulation due to a defect in the maintenance/progression, but not initiation, of activation signals. More importantly, GATA-3-deficient CD8+ T cells were less efficient in killing antigen-bearing tumor cells in vivo. Taken together, our data further expand the role of GATA-3 in T cells.
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