T Cell-Intrinsic CX3CR1 Marks the Most Differentiated Effector CD4+ T Cells, but Is Largely Dispensable for CD4+ T Cell Responses during Chronic Viral Infection.
T Cell-Intrinsic CX3CR1 Marks the Most Differentiated Effector CD4+ T Cells, but Is Largely Dispensable for CD4+ T Cell Responses during Chronic Viral Infection.
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DOI：
10.4049/immunohorizons.2000059
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发表时间：
2020-11-10
期刊：
影响因子：
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通讯作者：
Watts, Tania H
中科院分区：
文献类型：
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作者：
Batista, Nathalia V;Chang, Yu-Han;Watts, Tania H
CD4+ T细胞在慢性病毒感染中发挥关键作用，但调节这些反应的因素仍然不完全确定。在慢性感染淋巴细胞性脉络丛脑膜炎病毒克隆13 （LCMV13）的小鼠中，TNFR家族成员GITR在允许T细胞积聚和病毒控制中发挥关键的CD4+ T细胞内在作用。此前，对LCMV13感染第3天小鼠脾脏中分选的GITR+/+和GITR-/- T细胞的RNA测序发现，CD4+ T细胞中趋化因子受体CX3CR1因GITR信号传导而升高。在这项研究中，我们评估了CX3CR1在LCMV13感染期间对CD4+ T细胞的作用。Ag刺激后，CX3CR1在Ag特异性CD4+ T细胞上被诱导表达，GITR信号进一步提高CX3CR1的表达水平。CX3CR1是分化程度最高的T-bethi， Th1效应群体。与CX3CR1+/+细胞相比，过养转移的CX3CR1-/- SMARTA细胞每细胞T-bet和ifn - γ的表达略有降低，但在脾脏、肺或肝脏的积累没有缺陷。在用CX3CR1+/+和CX3CR1-/-骨髓重建的混合辐射嵌合体中，与CX3CR1-/- T细胞相比，CX3CR1+/+ CD4+ T细胞在组织驻留记忆T细胞数量上出现了边际缺陷。CX3CR1可能会限制组织驻留记忆T细胞表型的获得，因为它会增加T-bet表达，尽管这些小的影响不太可能具有主要的生物学意义。综上所述，这些研究表明CX3CR1标志着分化程度最高的CD4+ Th1效应群体，但在慢性病毒感染期间，CX3CR1在很大程度上是CD4+ T细胞应答所不可缺少的。
CD4+ T cells play critical roles during chronic viral infections, but the factors that regulate these responses remain incompletely defined. During chronic infection of mice with lymphocytic choriomeningitis virus clone 13 (LCMV13), the TNFR family member GITR plays a critical CD4+ T cell-intrinsic role in allowing T cell accumulation and viral control. Previously, RNA sequencing of GITR+/+ and GITR-/- T cells sorted from the spleen of mice at day 3 of LCMV13 infection identified the chemokine receptor CX3CR1 as increased by GITR signaling in CD4+ T cells. In this study, we evaluated the role of CX3CR1 on CD4+ T cells during LCMV13 infection. CX3CR1 expression is induced on Ag-specific CD4+ T cells upon Ag stimulation, and GITR signaling further increases the level of CX3CR1 expression. CX3CR1 marks the most differentiated T-bethi, Th1 effector population. Adoptively transferred CX3CR1-/- SMARTA cells had slightly reduced expression of T-bet and IFN-gamma per cell compared with their CX3CR1+/+ counterparts but showed no deficit in accumulation in the spleen, lung, or liver. In mixed-radiation chimeras reconstituted with CX3CR1+/+ and CX3CR1-/- bone marrow, CX3CR1+/+ CD4+ T cells showed a marginal deficit in tissue-resident memory T cell numbers compared with the CX3CR1-/- T cells. CX3CR1 may limit acquisition of the tissue-resident memory T cell phenotype because of its effects on increasing T-bet expression, albeit these small effects are unlikely to be of major biological significance. Taken together, these studies show that CX3CR1 marks the most highly differentiated CD4+ Th1 effector population but is largely dispensable for CD4+ T cell responses during chronic viral infection.