Regulating type 1 IFN effects in CD8 T cells during viral infections: changing STAT4 and STAT1 expression for function

Regulating type 1 IFN effects in CD8 T cells during viral infections: changing STAT4 and STAT1 expression for function
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DOI：
10.1182/blood-2012-05-428672
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发表时间：
2012-11-01
期刊：
BLOOD
影响因子：
20.3
通讯作者：
Biron, Christine A.
Biron, Christine A.
中科院分区：
医学1区
文献类型：
--
作者：
Gil, M. Pilar;Ploquin, Mickael J. Y.;Biron, Christine A.

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1 型 IFN 可以有条件地激活所有信号转导子和转录分子 (STAT) 激活子，包括 STAT4。然而，最典型的信号传导途径使用 STAT1，并且 1 型 IFN 对细胞增殖的抑制是 STAT1 依赖性的。我们报告说，1 型 IFN 可以基本刺激 CD8 T 细胞中的 STAT1 和 STAT4 依赖性效应，但 CD8 T 细胞对淋巴细胞性脉络膜脑膜炎病毒感染的小鼠做出反应，导致 STAT4 表达升高，STAT1 表达降低，这对改变 1 型 IFN 暴露的影响具有显着影响。与 STAT1 相比，该表型与 STAT4 的 1 型 IFN 优先激活相关。通过 TCR 的刺激诱导 STAT4 表达升高，而 STAT4 是抗原特异性 CD8 T 细胞峰值扩增、低 STAT1 水平和抵抗 1 型 IFN 介导的增殖抑制所必需的。因此，我们发现了一种调节 CD8 T 细胞中 1 型 IFN 暴露后果的机制，其中 STAT4 作为驱动最佳抗原特异性反应和克服 STAT1 依赖性增殖抑制的关键分子。 （血。2012；120(18):3718-3728）
Type 1 IFNs can conditionally activate all of the signal transducers and activators of transcription molecules (STATs), including STAT4. The best-characterized signaling pathways use STAT1, however, and type 1 IFN inhibition of cell proliferation is STAT1 dependent. We report that type 1 IFNs can basally stimulate STAT1- and STAT4- dependent effects in CD8 T cells, but that CD8 T cells responding to infections of mice with lymphocytic choriomenigitis virus have elevated STAT4 and lower STAT1 expression with significant consequences for modifying the effects of type 1 IFN exposure. The phenotype was associated with preferential type 1 IFN activation of STAT4 compared with STAT1. Stimulation through the TCR induced elevated STAT4 expression, and STAT4 was required for peak expansion of antigen-specific CD8 T cells, low STAT1 levels, and resistance to type 1 IFN-mediated inhibition of proliferation. Thus, a mechanism is discovered for regulating the consequences of type 1 IFN exposure in CD8 T cells, with STAT4 acting as a key molecule in driving optimal antigen-specific responses and overcoming STAT1-dependent inhibition of proliferation. (Blood. 2012;120(18):3718-3728)