title: 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.
authors: Department of Hepatology, Peking University People's Hospital, Beijing 100044, China.
authors: Hui
authors: H
authors: Ma
authors: Heng-Hui
authors: HH
authors: Zhang
authors: Lai
authors: L
authors: Wei
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004279:DNA, Viral / Q000097:blood; D005260:Female; D051858:Forkhead Transcription Factors / Q000032:analysis*; D006509:Hepatitis B / Q000188:drug therapy / Q000276:immunology*; D006513:Hepatitis B e Antigens / Q000097:blood*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D061026:Programmed Cell Death 1 Receptor / Q000032:analysis*; D011994:Recombinant Proteins / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D006513:Hepatitis B e Antigens; D000077190:Interferon alpha-2; D016898:Interferon-alpha; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C417083:peginterferon alfa-2b