Cytokine-Dependent Induction of CD4+ T cells with Cytotoxic Potential during Influenza Virus Infection
Cytokine-Dependent Induction of CD4+ T cells with Cytotoxic Potential during Influenza Virus Infection
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DOI：
10.1128/jvi.01461-13
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发表时间：
2013-11-01
影响因子：
5.4
通讯作者：
Sun, Jie
中科院分区：
文献类型：
--
作者：
Hua, Laiqing;Yao, Shuyu;Sun, Jie
最近的证据已经确定了颗粒酶B和穿孔素表达的CD 4（+）T细胞在抗病毒免疫中的作用。然而，在体内细胞因子的线索和下游的途径，这些细胞的分化还不清楚。在这里，我们已经确定了具有细胞毒性潜力的CD 4（+）T细胞在流感病毒感染期间在感染部位特异性诱导。体内具有细胞毒性潜能的CD 4（+）T细胞的发育依赖于STAT 2依赖性I型干扰素信号传导和白细胞介素-2/白细胞介素-2受体α通路的协作，以诱导转录因子T-bet和Blimp-1。我们发现Blimp-1促进T-bet与CD 4（+）T细胞中溶细胞基因启动子的结合，并且是体外和体内产生的具有细胞毒性潜力的CD 4（+）T细胞的溶细胞功能所必需的。因此，我们的数据定义了在急性呼吸道病毒感染过程中，这种功能性细胞毒性Th亚群在体内发展的调控的分子基础。这些细胞的功能的潜在影响进行了讨论。
Recent evidence has identified the role of granzyme B- and perforin-expressing CD4(+) T cells with cytotoxic potential in antiviral immunity. However, the in vivo cytokine cues and downstream pathways governing the differentiation of these cells are unclear. Here, we have identified that CD4(+) T cells with cytotoxic potential are specifically induced at the site of infection during influenza virus infection. The development of CD4(+) T cells with cytotoxic potential in vivo was dependent on the cooperation of the STAT2-dependent type I interferon signaling and the interleukin-2/interleukin-2 receptor alpha pathway for the induction of the transcription factors T-bet and Blimp-1. We showed that Blimp-1 promoted the binding of T-bet to the promoters of cytolytic genes in CD4(+) T cells and was required for the cytolytic function of the in vitro-and in vivo-generated CD4(+) T cells with cytotoxic potential. Thus, our data define the molecular basis of regulation of the in vivo development of this functionally cytotoxic Th subset during acute respiratory virus infection. The potential implications for the functions of these cells are discussed.