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Frequency of T-cell FoxP3+ Treg and CD4+/CD8+ PD-1 expression is related to HBeAg seroconversion in hepatitis B patients on pegylated interferon
Authors:MA Hui  ZHANG Heng-hui  WEI Lai
Institution:1. Department of Hepatology Peking University People's Hospital, Beijing 100044, China
2. Peking University Hepatology Institute Peking University People's Hospital, Beijing 100044, China
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 (PeglFN)α-2b treatment.Methods Patients received PeglFNα-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 PeglFNα-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.
Keywords:chronic hepatitis B  dendritic cells  pegylated interferon α-2b  programmed death 1  regulatory T cell
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