Circulating CD4+ CD25+ regulatory T cells correlate with chronic hepatitis B infection.
Circulating CD4+ CD25+ regulatory T cells (Tregs) have been demonstrated to maintain immunotolerance and suppress the antigen-specific or antigen-non-specific T-cell responses, but their role in chronic hepatitis B (CHB) infection in humans has not been well characterized. In this study, we analysed the frequency and phenotypic characteristics of CD4+ CD25+ Tregs in patients of different hepatitis B virus (HBV) infection status, and investigated the effect of Tregs on antiviral immune responses in CHB patients, and the mechanism of this effect. A total of 137 subjects, including 79 CHB patients, 26 asymptomatic HBV carriers (ASCs), 12 acute hepatitis B (AHB) patients and 20 healthy controls, were enrolled in the study. We found that the frequency of CD4+ CD25(high) Tregs in AHB patients was comparable to that in healthy controls, while it was significantly increased in CHB patients. CD4+ CD25+ Tregs produced interleukin (IL)-10 but little or no interferon (IFN)-gamma under anti-CD3 stimulation. In CHB patients, the frequency of CD4+ CD25(high) Tregs positively correlated with serum viral load, and the Tregs were capable of suppressing the proliferation and IFN-gamma production of autologous peripheral blood mononuclear cells (PBMC) mediated by HBV antigen stimulation in vitro. However, combined administration of anti-programmed death-1 (PD-1) and anti-cytotoxic lymphocyte antigen-4 (CTLA-4) monoclonal antibody slightly enhanced the cellular proliferation and significantly increased the IFN-gamma production of PBMC cocultured with Tregs at a ratio of 2:1. Thus, the frequency of circulating CD4+ CD25+ Tregs is increased in patients with CHB, and this may play an important role in viral persistence by modulating virus-specific immune responses.
Peng
Guoping
G
Key Laboratory of Health Ministry, Institute of Infectious Diseases, First Affiliated Hospital, Medical College, Zhejiang University, Zhejiang, China.
Li
Shuping
S
Wu
Wei
W
Sun
Zhen
Z
Chen
Yiqiong
Y
Chen
Zhi
Z
D000208:Acute Disease; D000328:Adult; D002353:Carrier State / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D051858:Forkhead Transcription Factors / Q000097:blood; D006509:Hepatitis B / Q000276:immunology; D006515:Hepatitis B virus / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000276:immunology* / Q000821:virology; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D016130:Immunophenotyping; D053645:Interleukin-2 Receptor alpha Subunit / Q000097:blood; D008297:Male; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D019562:Viral Load
D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit