CD8⁺ T cells responding to chronic infection adapt an altered differentiation program that provides some restraint on pathogen replication yet limits immunopathology. This adaptation is imprinted in stem-like cells and propagated to their progeny. Understanding the 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-specific stem-like CD8⁺ T cells and that one of its ligands, CXCL10, regulates the persistence and heterogeneity of responding CD8⁺ T cells in spleens of mice chronically infected with lymphocytic choriomeningitis virus. CXCL10 is produced by inflammatory monocytes and fibroblasts of the splenic red pulp, where it grants stem-like cells access to signals promoting differentiation and 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.

对慢性感染做出反应的CD8 ⁺ T 细胞会适应改变的分化程序，该程序对病原体复制提供一定的限制，但也限制了免疫病理学。这种适应被印在干细胞样细胞中并传播给它们的后代。^{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。在这里，我们发现趋化因子受体 CXCR3 在病毒特异性干细胞样 CD8 ⁺ T 细胞上高表达，其配体之一 CXCL10 调节慢性感染小鼠脾脏中响应 CD8 ⁺ T 细胞的持久性和异质性。淋巴细胞性脉络膜脑膜炎病毒。CXCL10 由脾红髓的炎症单核细胞和成纤维细胞产生，它使干细胞样细胞能够获得促进分化的信号，并限制它们暴露于白髓中的促生存生态位。因此，Cxcl10 ^{-/−小鼠的功能性 CD8 +} T 细胞反应更强，并且与较低的病毒设定点相关。