近日，美国马萨诸塞州综合医院Andrew D. Luster及其课题组发现，CXCL10趋化因子调节慢性感染期间CD8⁺T细胞反应的异质性。2021年11月29日，国际知名学术期刊《免疫》在线发表了这一成果。

研究人员发现，趋化因子受体CXCR3在病毒特异性干细胞样CD8⁺T细胞上高度表达，其配体之一CXCL10调节慢性感染淋巴细胞性脉络丛脑膜炎病毒的小鼠脾脏中反应性CD8⁺T细胞的持久性和异质性。CXCL10由脾脏红髓的炎症单核细胞和成纤维细胞产生，在那里它使干细胞获得促进分化的信号，并限制它们暴露于白髓中有利于生存的微环境。因此，Cxcl10^-/-小鼠的功能性CD8⁺T细胞反应更大。

据介绍，应对慢性感染的CD8⁺T细胞适应了一种改变的分化程序，对病原体的复制提供了一些限制，但也限制了免疫病理学。这种适应性在干细胞中打上了印记，并传播到它们的后代。了解慢性感染中CD8⁺T细胞分化的分子控制具有重要的治疗意义。

附：英文原文

Title: CXCL10 chemokine regulates heterogeneity of the CD8+ T cell response and viral set point during chronic infection

Author: Aleksandra J. Ozga, Melvyn T. Chow, Mateus E. Lopes, Rachel L. Servis, Mauro Di Pilato, Philippe Dehio, Jeffrey Lian, Thorsten R. Mempel, Andrew D. Luster

Issue&Volume: 2021-11-29

Abstract: CD8+ T cells responding to chronic infection adapt an altered differentiation programthat provides some restraint on pathogen replication yet limits immunopathology. Thisadaptation is imprinted in stem-like cells and propagated to their progeny. Understandingthe molecular control of CD8+ T cell differentiation in chronic infection has important therapeutic implications.Here, we find that the chemokine receptor CXCR3 is highly expressed on viral-specificstem-like CD8+ T cells and that one of its ligands, CXCL10, regulates the persistence and heterogeneityof responding CD8+ T cells in spleens of mice chronically infected with lymphocytic choriomeningitisvirus. CXCL10 is produced by inflammatory monocytes and fibroblasts of the splenicred pulp, where it grants stem-like cells access to signals promoting differentiationand limits their exposure to pro-survival niches in the white pulp. Consequently,functional CD8+ T cell responses are greater in Cxcl10/ mice and are associated with a lower viral set point.

DOI: 10.1016/j.immuni.2021.11.002

Source: https://www.cell.com/immunity/fulltext/S1074-7613(21)00493-3