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Paper Information

Journal:   HEPATITIS MONTHLY   2007 , Volume 7 , Number 4; Page(s) 183 To 200.
 
Paper: 

ACUTE EXACERBATIONS OF CHRONIC HEPATITIS B ARE ACCOMPANIED BY DECLINE OF CORE ANTIGEN-SPECIFIC REGULATORY T-CELL FREQUENCIES: IMPLICATIONS FOR SUCCESSFUL ANTI-HBV TREATMENTS

 
 
Author(s):  TSAI S.L.*, WANG S.L., FENG I.C., KUO H.T., KOAY L.B., SHEU M.J., LEE CHUAN, SUN C.S., WU K.T., LIN CH.Y.
 
* LIVER RESEARCH UNIT, DEPARTMENT OF MEDICAL RESEARCH, CHI. MEI. MEDICAL CENTER, 901 CHUNG HWA ROAD, YOUNG-KANG CITY, TAINAN, 710 TAIWAN
 
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.

 
Keyword(s): CHRONIC HEPATITIS B, ACUTE EXACERBATION, REGULATORY T CELL, SUSTAINED REMISSION
 
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