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Dichotomous Expression of TNF Superfamily Ligands on Antigen-Presenting Cells Controls Post-priming Anti-viral CD4+ T Cell Immunity
Immunity ( IF 25.5 ) Pub Date : 2017-11-14 , DOI: 10.1016/j.immuni.2017.10.014
Yu-Han Chang , Kuan Chung Wang , Kuan-Lun Chu , Derek L. Clouthier , Anh T. Tran , Miguel S. Torres Perez , Angela C. Zhou , Ali A. Abdul-Sater , Tania H. Watts

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.



中文翻译:

TNF超家族配体在抗原呈递细胞上的二分表达控制了启动后抗病毒CD4 + T细胞的免疫力

在慢性病毒感染的早期,T细胞抗原呈递细胞(APC)的相互作用对于确定病毒设定点和疾病结局至关重要,但是尚不清楚不同的APC亚型如何以及何时促成这些结局。TNF受体超家族(TNFRSF)成员GITR对于CD4 + T细胞积累和控制慢性淋巴细胞性脉络膜脑膜炎病毒(LCMV)具有重要意义。我们发现I型干扰素(IFN-I)主要在单核细胞衍生的APC上诱导TNFSF配体GITRL,4-1BBL,OX40L和CD70,在经典树突状细胞(cDCs)上主要诱导CD80和CD86。在Lyz2 +细胞中功能低下的GITRL小鼠的LCMV特异性CD4 + T细胞积聚减少,病毒载量增加。CD4 +中的GITR信号在启动以上调OX40,CD25和趋化因子受体CX3CR1后出现T细胞。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cDC和单核细胞衍生的APC在调节T细胞扩增方面的分工。

更新日期:2017-11-14
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