Acute Exacerbations of Chronic Hepatitis B Are Accompanied by Decline of Core Antigen-Specific Regulatory T-Cell Frequencies: Implications for Successful Anti-HBV Treatments

AUTHORS

Sun -Lung Tsai 1 , * , Shih Ling Wang 2 , I -Che Feng 2 , Hsing -Tao Kuo 2 , Lok -Beng Koay 2 , Ming -Jen Sheu 2 , Chuan Lee 2 , Chi -Shu Sun 2 , Kuan -Ta Wu 2 , Chin -Yi Lin 2

1 Research Unit, Department of Medical Research, Chi Mei Medical Center & Hepatogastroenterology Section, Department of Internal Medicine, Chi Mei Medical Center, [email protected], Taiwan

2 Liver Research Unit, Department of Medical Research, Chi Mei Medical Center, Taiwan

How to Cite: Tsai S, Wang S, Feng I, Kuo H, Koay L, et al. Acute Exacerbations of Chronic Hepatitis B Are Accompanied by Decline of Core Antigen-Specific Regulatory T-Cell Frequencies: Implications for Successful Anti-HBV Treatments, Hepat Mon. Online ahead of Print ; 7(4):183-200.

ARTICLE INFORMATION

Hepatitis Monthly: 7 (4); 183-200
Article Type: Research Article
Received: November 22, 2007
Accepted: December 25, 2007

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Abstract

Background and Aims: Acute exacerbations (AEs) of perinatally-acquired chronic hepatitis B (CHB) are accompanied by increased T cell responses to hepatitis B core and e antigens (HBcAg & HBeAg). Naturally-arising forkhead transcription factor Foxp3 (forkhead box p3)-expressing CD4+CD25+ regulatory T (Treg) cells are thought to be important in the control of infectious diseases. This study aimed to investigate whether HBcAg-specific Treg cells play a role in modulating spontaneous AEs and in influencing the outcome of anti-hepatitis B virus (HBV) treatments.

Methods: The SYFPEITHI scoring system was employed to predict epitope peptides on HBcAg overlapping with HBeAg for the construction of peptide-HLA class II tetramers to measure HBcAg-specific Treg cell frequencies (Treg f ).

Results: HBcAg-specific Treg f declined significantly in association with increased HBcAg-specific cytotoxic T lymphocyte frequencies during spontaneous AEs without treatment. Vigorous in vitro expansion of CD4+CD25+ Treg cells from CHB patients responding to HBcAg and/or its peptides plus interleukin-2 (IL-2) was consistently detected. Depletion of Treg cells from peripheral blood mononuclear cells enhanced proliferation to HBcAg. In contrast, patients with AEs who received anti-HBV treatments with oral nucleoside analogues or interferon-alpha injection revealed that more post-treatment increase of HBcAg-specific Treg f correlated with a higher sustained remission rate to the therapy.

Conclusions: These data indicate that HBcAg-specific Treg cells from perinatally-acquired CHB patients are proliferative to HBcAg and its peptides and exhibit suppressor activity. They play a crucial role in modulating spontaneous AEs and in successful anti-HBV treatments.

Keywords

Chronic Hepatitis B Acute Exacerbation Regulatory T Cell Sustained Remission

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