C-X-C chemokine receptor type 5CD8 T cells as immune regulators in hepatitis Be antigen-positive chronic hepatitis B under interferon-alpha treatment.

BACKGROUND

C-X-C chemokine receptor type 5 (CXCR5)CD8 T cells represent a unique immune subset with dual roles, functioning as cytotoxic cells in persistent viral infections while promoting B cell responses. Despite their importance, the specific role of CXCR5CD8 T cells in chronic hepatitis B (CHB), particularly during interferon-alpha (IFN-α) treatment, is not fully understood. This study aims to elucidate the relationship between CXCR5CD8 T cells and sustained serologic response (SR) in patients undergoing 48 weeks of pegylated IFN-α (peg-IFN-α) treatment for CHB.

AIM

To elucidate the relationship between CXCR5CD8 T cells and sustained SR in patients undergoing 48 weeks of peg-IFN-α treatment for CHB.

METHODS

This study enrolled 60 patients with hepatitis Be antigen (HBeAg)-positive CHB undergoing 48 weeks of peg-IFN-α treatment. Participants were assessed for eligibility based on criteria such as persistent HBsAg-positive status for at least six months, HBeAb-negative, hepatitis B virus DNA levels exceeding 2 × 10 copies/mL, and alanine aminotransferase (ALT) levels between 2 and 10 times the upper limit of normal. Blood samples were collected at baseline and at weeks 12, 24, 48, and a 24-week treatment-free follow-up (week 72) to measure serum interleukin (IL)-21 concentration ELISA and to analyze CXCR5 and programmed death-ligand 1 (PD-L1) expression on CD8 T cells by flow cytometry, CXCR5 is a chemokine receptor that directs immune cells to specific tissues, while PD-L1 is a protein that regulates immune responses by inhibiting T cell activity.

RESULTS

Patients with CHB exhibited significantly lower levels of circulating CXCR5CD8 T cells compared to healthy controls ( < 0.01). Notably, CXCR5+CD8+ T cells were prominently expressed in patients who achieved sustained SR compared to non-SR (NSR). A significant correlation was observed between CXCR5 and PD-L1 expression ( = -0.189, = 0.002). However, there was no significant correlation between serum IL-21 levels and CXCR5CD8 lymphocytes ( = -0.03, = 0.625) or serum ALT levels ( = 0.026, = 0.678).

CONCLUSION

The enhanced expression of CXCR5CD8 T cells in patients achieving HBeAg seroconversion during IFN-α treatment suggests that these cells play a crucial role in antiviral immune responses against hepatitis B. This study highlights the potential of CXCR5CD8 T cells as immune regulators in CHB, which may inform future therapeutic strategies to optimize antiviral treatments.