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 | Sun -Lung Tsai | en |
| Author | Shih Ling Wang | en |
| Author | I -Che Feng | en |
| Author | Hsing -Tao Kuo | en |
| Author | Lok -Beng Koay | en |
| Author | Ming -Jen Sheu | en |
| Author | Chuan Lee | en |
| Author | Chi -Shu Sun | en |
| Author | Kuan -Ta Wu | en |
| Author | Chin -Yi Lin | en |
| Issued Date | 2007-12-31 | en |
| 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. | en |
| DOI | https://doi.org/ | en |
| Keyword | Chronic Hepatitis B | en |
| Keyword | Acute Exacerbation | en |
| Keyword | Regulatory T Cell | en |
| Keyword | Sustained Remission | en |
| Publisher | Brieflands | en |
| Title | Acute Exacerbations of Chronic Hepatitis B Are Accompanied by Decline of Core Antigen-Specific Regulatory T-Cell Frequencies: Implications for Successful Anti-HBV Treatments | en |
| Type | Research Article | en |