CXCR3 regulates stem and proliferative CD8+ T cells during chronic infection by promoting interactions with DCs in splenic bridging channels.
CXCR3 regulates stem and proliferative CD8+ T cells during chronic infection by promoting interactions with DCs in splenic bridging channels.
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CXCR3通过促进与脾桥接通道中DC的相互作用来调节慢性感染期间的干细胞和增殖性CD8+ T细胞。
DOI：
10.1016/j.celrep.2021.110266
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发表时间：
2022-01-18
期刊：
影响因子：
8.8
通讯作者：
Robey EA
中科院分区：
文献类型：
--
作者：
Bangs DJ;Tsitsiklis A;Steier Z;Chan SW;Kaminski J;Streets A;Yosef N;Robey EA
在持续感染期间，效应CD8+ T细胞的产生需要一个稳定的干细胞库，这些干细胞库可以通过增殖的中间群体产生效应细胞。在以T细胞衰竭为标志的感染模型中，这一过程可以通过检查点阻断短暂诱导，但在慢性感染细胞内原生动物弓形虫的小鼠中会自发发生。我们观察到寄生虫特异性T细胞亚群的不同位置，这意味着分化与脾脏解剖壁龛之间存在联系。T细胞上趋化因子受体CXCR3的缺失并不会阻止白髓向红髓的迁移，但会减少与CXCR3配体产生的树突状细胞（dc）的相互作用，并损害记忆向中间过渡，导致红髓中记忆T细胞的积累。因此，在红髓迁移过程中，CXCR3增加了T细胞对诱导分化信号的暴露，为调节效应细胞在响应环境信号时的分化提供了一个动态机制。Bangs等人报道，在慢性感染期间发现的CD8+ T细胞的不同亚群占据了脾脏的不同区域。CXCR3调节T细胞的分化，但不调节其迁移。相反，CXCR3促进T细胞与桥接通道中产生配体的dc的相互作用，导致效应分化。
Production of effector CD8+ T cells during persistent infection requires a stable pool of stem-like cells that can give rise to effector cells via a proliferative intermediate population. In infection models marked by T cell exhaustion, this process can be transiently induced by checkpoint blockade but occurs spontaneously in mice chronically infected with the protozoan intracellular parasite Toxoplasma gondii. We observe distinct locations for parasite-specific T cell subsets, implying a link between differentiation and anatomical niches in the spleen. Loss of the chemokine receptor CXCR3 on T cells does not prevent white pulp-to-red pulp migration but reduces interactions with CXCR3 ligand-producing dendritic cells (DCs) and impairs memory-to-intermediate transition, leading to a buildup of memory T cells in the red pulp. Thus, CXCR3 increases T cell exposure to differentiation-inducing signals during red pulp migration, providing a dynamic mechanism for modulating effector differentiation in response to environmental signals. Bangs et al. report that distinct subsets of CD8+ T cells found during chronic infection occupy distinct regions of the spleen. CXCR3 regulates differentiation of T cells but not their migration. Instead, CXCR3 promotes the interaction of T cells with ligand-producing DCs in bridging channels, resulting in effector differentiation.
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