Abstract
Hepatitis B surface antigen (HBsAg) seroconversion is considered the optimal outcome of the treatment of chronic hepatitis B virus (HBV) infection. In this study, we aimed to determine the cellular and molecular mechanisms by which pegylated interferon alpha (PEG-IFN-α) improves the seroconversion rate in patients with chronic hepatitis B (CHB).
Flow cytometry was performed using circulating T follicular helper (TFH) cells from 15 healthy individuals and 45 patients with CHB presenting different treatment responses [complete response group (CRG), incomplete response group (ICRG), and nonresponse group (NRG)] to the standard 48-week regimen of PEG-IFN-α monotherapy to examine the significance of circulating TFH cells in the therapeutic response of patients with CHB to PEG-IFN-α. In addition, the capacities of different TFH subsets to activate B cells and stimulate IgG production were assessed by performing coculture experiments.
Longitudinal analysis revealed specific and significant increases in the numbers of CD40L
CD4
CXCR5
TFH cells in the CRG compared with the NRG and ICRG. According to the results of in vitro coculture experiments, blocking CD40-CD40L signaling, but not ICOS-ICOSL signaling, specifically inhibits B-cell activation and IgG production. HBV may impair TFH cell function by enhancing inhibitory regulatory T-cell activity. Transcriptome analysis further revealed the upregulation of CD40L, but not of ICOS, in TFH cells isolated from the CRG.
TFH cells, particularly those with CD40L expression, stimulate B-cell differentiation and improve the HBsAg seroconversion rate in patients with CHB treated with PEG-IFN-α monotherapy.