Frequency of T-cell FoxP3⁺ Treg and CD4⁺/CD8⁺ PD-1 expression is related to HBeAg seroconversion in hepatitis B patients on pegylated interferon.
- Author:
Hui MA
1
;
Heng-Hui ZHANG
;
Lai WEI
Author Information
- Publication Type:Journal Article
- MeSH: Adult; Antiviral Agents; therapeutic use; CD4-Positive T-Lymphocytes; immunology; CD8-Positive T-Lymphocytes; immunology; DNA, Viral; blood; Female; Forkhead Transcription Factors; analysis; Hepatitis B; drug therapy; immunology; Hepatitis B e Antigens; blood; Humans; Interferon-alpha; therapeutic use; Male; Polyethylene Glycols; therapeutic use; Programmed Cell Death 1 Receptor; analysis; Recombinant Proteins; therapeutic use; T-Lymphocytes; immunology; T-Lymphocytes, Regulatory; immunology
- From: Chinese Medical Journal 2013;126(2):267-273
- CountryChina
- Language:English
-
Abstract:
BACKGROUNDHost 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.
METHODSPatients 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).
RESULTSIn 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.
CONCLUSIONSThe 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.