CXCR3high CD8+ T cells with naïve phenotype and high capacity for IFN‐γ production are generated during homeostatic T‐cell proliferation.

Abstract: Naïve phenotype (NP) T cells spontaneously initiate homeostatic proliferation (HP) as T‐cell output is reduced because of physiologic thymic involution with age. However, the effects of sustained HP on overall immune function are poorly understood. We demonstrated that the NP CD8⁺ T cell population in adult thymectomized mice showing accelerated HP has an increased capacity for TCR‐mediated interferon‐γ and tumor necrosis factor α production, which is attributed to an increase in CXCR3⁺ cells in the NP CD8⁺ T cell population. The CXCR3⁺ NP CD8⁺ T cells developed during persistent HP with a slow cell division rate, but rarely during robust antigen‐driven proliferation with a fast cell division rate. In ontogeny, the proportions of CXCR3⁺ cells in the NP CD8⁺ T cell population showed a biphasic profile, which was high at the newborn and aged stages. Upon transfer, CXCR3⁺ NP CD8⁺ T cells, but not CXCR3⁻ NP CD8⁺ T cells, potently enhanced Th17‐mediated inflammatory tissue reactions in vivo. Furthermore, CXCR3^high NP CD8⁺ T cells with similar features were also detected at variable levels in healthy human blood. These results suggest that CXCR3⁺ NP CD8⁺ T cells generated during physiological HP significantly impact overall immunity at the immunologically vulnerable neonatal and aged stages. [ABSTRACT FROM AUTHOR]