European Journal of Immunology · Jul 31, 2018

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

By Kato A, Takaori-Kondo A, Minato N et al.

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, CXCR3high 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.

doi.org/10.1002/eji.201747431Open accessPubMed 30058200Mechanisms