Cytomegalovirus (CMV) has evolved a unique virus-host relationship in the salivary glands (SGs) to sustain prolonged viral replication and hence chances for horizontal transmission. Previous reports have established a decisive role for IFNγ producing CD4+ T cells to control murine CMV (MCMV) infection in the SGs; however, micro-anatomical information regarding their mode of action is largely missing. Here, we provide a spatiotemporal analysis of defined antiviral immune actions that eventually culminate in control of lytic MCMV replication. CXCR3-mediated guidance of CD4+ T cells towards CXCL9 and CXCL10 expressing cells resulted in discrete clusters close to infection foci where they reported TCR engagement and produced IFNγ. These clusters occasionally contained CD11c+ antigen-presenting cells with engulfed virus-associated remnants, most likely apoptotic bodies from previously infected cells, enabling antigen presentation to CD4+ T cells. The induced IFNγ production in CD4+ T cell accumulations triggered IFNγR signaling in a confined perimeter, thereby inducing local, but not organ-wide protection, and allowing MCMV replication to continue at not yet protected sites. Combining experimental data with a mathematical model of the spatiotemporal dynamics of infection and CD4+ T cell dynamics revealed a scenario, in which ultimate MCMV control is achieved through accumulating sites of regionally-confined tissue protection.

中文翻译：

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CD4 + T细胞在局部产生的γ干扰素产生为鼠巨细胞病毒在唾液腺中的复制提供了空间

巨细胞病毒（CMV）已在唾液腺（SGs）中发展出独特的病毒-宿主关系，以维持延长的病毒复制，从而有机会进行水平传播。先前的报道已经确定了产生IFNγ的CD4 + T细胞在SGs中控制鼠CMV（MCMV）感染的决定性作用。然而，关于它们的作用方式的微观解剖学信息却大为缺失。在这里，我们提供了确定的抗病毒免疫作用的时空分析，最终最终导致了溶血性MCMV复制的控制。CXCR3介导的CD4 + T细胞朝向表达CXCL9和CXCL10的细胞的引导导致靠近感染灶的离散簇，在那里他们报告TCR参与并产生IFNγ。这些簇偶尔包含CD11c +抗原呈递细胞，并吞噬了与病毒相关的残留物，最有可能来自先前感染细胞的凋亡小体，从而使抗原呈递给CD4 + T细胞。CD4 + T细胞积聚中诱导的IFNγ产生在有限的周长内触发IFNγR信号传导，从而诱导局部但非器官范围的保护，并允许MCMV复制在尚未受保护的位点继续进行。将实验数据与感染时空动态和CD4 + T细胞动态的数学模型相结合，揭示了一种方案，其中通过累积区域受限组织保护位点来实现最终的MCMV控制。并允许MCMV复制在尚未受保护的站点上继续进行。将实验数据与感染时空动态和CD4 + T细胞动态的数学模型相结合，揭示了一种方案，其中通过累积区域受限组织保护位点来实现最终的MCMV控制。并允许MCMV复制在尚未受保护的站点上继续进行。将实验数据与感染的时空动态和CD4 + T细胞动态的数学模型相结合，揭示了一种方案，其中通过累积区域受限组织保护位点来实现最终的MCMV控制。