Frequency of T-cell FoxP3+ Treg and CD4+/CD8+ PD-1 expression is related to HBeAg seroconversion in hepatitis B patients on pegylated interferon

Abstract

Background Host immune responses against hepatitis B virus (HBV) induced by antiviral therapy play a crucial role in viral clearance. To further investigate the immune mechanisms underlying the differences between respondents and non-respondents, we analyzed myeloid dendritic cells (mDCs), plasmacytoid dendritic cells (pDCs), FoxP3+ regulatory T cells (FoxP3+ Treg) and programmed death 1 (PD-1) expression in CD4+/CD8+ T cells in chronic hepatitis B patients undergoing pegylated interferon (PegIFN)α-2b treatment. Methods Patients received PegIFNα-2b for 24 or 48 weeks, with follow-up at 24 weeks. The frequencies of mDCs, pDCs, FoxP3+ Treg, and PD-1 expression by CD4+/CD8+ T cells were evaluated by flow cytometry at baseline, weeks 4 and 12, end of treatment, and follow-up (12/24 weeks). Results In HBeAg seroconverters (respondents), the mDC relative frequency decreased at week 4 and then rebounded at week 12. The pDC relative frequency decreased consistently. In non-HBeAg seroconverters (non-respondents), both mDC and pDC frequencies decreased slightly. The FoxP3+ Treg relative frequency decreased during treatment and remained low during follow-up in respondents, while in non-respondents it decreased slightly during therapy but rebounded after discontinuation. In patients with HBeAg <17.55 PEI-U/ml at week 12 and <8.52 PEI-U/ml at week 24, the FoxP3+ Treg frequency decreased during treatment and at follow-up. In respondents, CD4+PD-1 and CD8+PD-1 levels decreased at week 4 and remained low at week 12. In non-respondents, PD-1 expression decreased at week 4 but rebounded at week 12. Conclusions The results indicate that the dynamic changes in DCs, FoxP3+ Treg frequency, and PD-1 expression by CD4+ and CD8+ T cells exhibit different trends in HBeAg and non-HBeAg seroconversion patients. During PegIFNα-2b treatment of chronic hepatitis B patients, these changes may be of predictive value for HBeAg seroconversion. HBsAg and HBeAg levels are related to FoxP3+ Treg frequency.