CD8 + T cell exhaustion contributes to viral persistence in patients with hepatitis B virus (HBV) infection. Emerging evidence identifies CXCR5 + CD8 + T cells as a distinct subset with dual antiviral and B-cell helper functions across disease contexts. Peripheral blood mononuclear cells from chronic HBV-infected patients were used to characterize the frequency, phenotype and functions of CXCR5 + CD8 + T cells using flow cytometry. A publicly available single-cell RNA sequencing (scRNA-seq) dataset was used to elucidate transcriptional profiles. Chronic hepatitis B (CHB) patients exhibited expanded CXCR5 + CD8 + T cells that inversely correlated with hepatitis B surface antigen (HBsAg) and HBV DNA levels ( P < 0.05). Despite elevated inhibitory receptors, these cells maintained enhanced IL-2 production, preserved IFN-γ, TNF-α and perforin output, and reduced granzyme B compared with CXCR5 - counterparts. Meanwhile, CXCR5 + subsets express costimulatory molecules and secrete higher levels of IL-21 to promote B-cell responses. scRNA-seq analysis confirmed these effector-helper features. HBV-specific CXCR5 + CD8 + T cells secrete more IFN-γ and TNF-α relative to CXCR5 - subsets. Furthermore, PD-1 expressing CXCR5 + CD8 + T cells expressed higher memory related molecule and produced more effector cytokines. In conclusion, CXCR5 + CD8 + T cells play a potential role in viremia control in CHB patients via both direct antiviral effector function and the modulation of humoral immunity. PD-1 in these cells seems not to show exhaustion characteristics. Thus, strategies that booster CXCR5 + CD8 + T cell responses may help control HBV infection.
Liu et al. (Sun,) studied this question.