Circulating PD-1^hiCXCR5⁺CD4⁺ T cells are associated with a decrease in hepatitis B surface antigen levels in patients...

Given the B helper function of follicular T helper (Tfh) cells and peripheral T helper (Tph) cells, we researched the roles of circulating PD-1^hiCXCR5⁺CD4⁺ T cells and PD-1^hiCXCR5^-CD4⁺ T cells in the decrease in hepatitis B surface antigen (HBsAg) levels and hepatitis B virus (HBV) clearance in patients with chronic hepatitis B (CHB). In the present study, the frequencies of PD-1^hiCXCR5⁺CD4⁺ T cells and PD-1^hiCXCR5^-CD4⁺ T cells measured by flow cytometry were significantly higher in patients with CHB than that in healthy controls (HCs). Our longitudinal study did not reveal significant differences in the frequencies of both cell populations before and after 48 weeks of peginterferon-α (PEG-IFN-α) therapy. However, repeated measurements of serum HBsAg levels revealed significantly lower HBsAg levels over time in patients who exhibited an increase in the frequency of PD-1^hiCXCR5⁺CD4⁺ T cells after PEG-IFN-α treatment. In addition, the increase in the frequency of PD-1^hiCXCR5⁺CD4⁺ T cells exerted a significant positive effect on the HBsAg level, which decreased to ≤2 Log₁₀ IU/mL and ≤3 Log₁₀ IU/mL at the end of treatment. However, no significant difference in HBsAg levels was observed over time, regardless of whether the frequency of circulating PD-1^hiCXCR5^-CD4⁺ T cells was elevated. Repeated measurements of the HBV DNA concentration did not show significant differences between patients exhibiting changes in the frequencies of these two cell subsets and HBV DNA clearance. Overall, circulating PD-1^hiCXCR5⁺CD4⁺ T cells and PD-1^hiCXCR5^-CD4⁺ T cells may be involved in the immune landscape of patients with a chronic HBV infection. Moreover, PD-1^hiCXCR5⁺CD4⁺ T cells are associated with decreased HBsAg levels in patients with CHB who are receiving peginterferon-α therapy.