Dichotomous Expression of TNF Superfamily Ligands on Antigen-Presenting Cells Controls Post-priming Anti-viral CD4+ T Cell Immunity
Dichotomous Expression of TNF Superfamily Ligands on Antigen-Presenting Cells Controls Post-priming Anti-viral CD4+ T Cell Immunity
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DOI：
10.1016/j.immuni.2017.10.014
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发表时间：
2017-11-21
期刊：
影响因子：
32.4
通讯作者：
Watts, Tania H.
中科院分区：
文献类型：
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作者：
Chang, Yu-Han;Wang, Kuan Chung;Watts, Tania H.
慢性病毒感染早期的T细胞抗原呈递细胞（APC）相互作用对于确定病毒设定点和疾病结果至关重要，但不同APC亚型如何以及何时影响这些结果尚不清楚。TNF受体超家族（TNFRSF）成员GITR对CD4(+) T细胞积累和慢性淋巴细胞性脉络丛脑膜炎病毒（LCMV）的控制很重要。我们发现I型干扰素（IFN-I）诱导的TNFSF配体GITRL、4-1BBL、OX40L和CD70主要作用于单核细胞来源的apc， CD80和CD86主要作用于经典树突状细胞（cDCs）。Lyz2（+）细胞GITRL功能低下的小鼠lcmv特异性CD4(+) T细胞积累减少，病毒载量增加。CD4(+) T细胞中的GITR信号在启动后上调OX40、CD25和趋化因子受体CX3CR1。因此，IFN-I（信号3）诱导了CD4(+) T细胞积累的启动后检查点（信号4），揭示了cDCs和单核细胞来源的APCs在调节T细胞扩增方面的分工。
T cell antigen-presenting cell (APC) interactions early during chronic viral infection are crucial for determining viral set point and disease outcome, but how and when different APC subtypes contribute to these outcomes is unclear. The TNF receptor superfamily (TNFRSF) member GITR is important for CD4(+) T cell accumulation and control of chronic lymphocytic choriomeningitis virus (LCMV). We found that type I interferon (IFN-I) induced TNFSF ligands GITRL, 4-1BBL, OX40L, and CD70 predominantly on monocyte-derived APCs and CD80 and CD86 predominantly on classical dendritic cells (cDCs). Mice with hypofunctional GITRL in Lyz2(+) cells had decreased LCMV-specific CD4(+) T cell accumulation and increased viral load. GITR signals in CD4(+) T cells occurred after priming to upregulate OX40, CD25, and chemokine receptor CX3CR1. Thus IFN-I (signal 3) induced a post-priming checkpoint (signal 4) for CD4(+) T cell accumulation, revealing a division of labor between cDCs and monocyte-derived APCs in regulating T cell expansion.