1. Hepatitis B virus (HBV) core antigen-specific regulatory T cells confer sustained remission to anti-HBV therapy in chronic hepatitis B with acute exacerbation
- Author
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Chin-Yih Lin, Ling-Yu Tang, Shih-Ling Wang, Jyh-Jou Chen, Ming-Jen Sheu, Hsing-Tao Kuo, I-Che Feng, Lok-Beng Koay, and Sun-Lung Tsai
- Subjects
Cytotoxicity, Immunologic ,Hepatitis B virus ,Immunology ,T-Cell Antigen Receptor Specificity ,Biology ,Antiviral Agents ,T-Lymphocytes, Regulatory ,Epitope ,Virus ,Immune tolerance ,Epitopes ,Hepatitis B, Chronic ,Antigen ,T-Lymphocyte Subsets ,medicine ,Immunology and Allergy ,Cytotoxic T cell ,Humans ,Cell Proliferation ,Hepatitis ,Immunosuppression Therapy ,Remission Induction ,Histocompatibility Antigens Class II ,virus diseases ,Forkhead Transcription Factors ,General Medicine ,Hepatitis B ,medicine.disease ,Virology ,Hepatitis B Core Antigens ,digestive system diseases ,HBcAg ,Epitope Mapping ,Liver Failure ,Protein Binding - Abstract
Acute exacerbations (AEs) of chronic hepatitis B (CH-B) are thought to be the result of breakdown of immune tolerance on the natural history of chronic hepatitis B virus (HBV) infection. Immune tolerance to HBV maintained in CH-B patients without hepatitis is under the control of the host's forkhead box p3-expressing regulatory T cells (Tregs). Its breakdown mimics the occurrence of autoimmune diseases. Severe AEs may lead to liver decompensation and mortalities. Consequently, AEs are currently the major therapeutic targets in patient treatment. In this study, we employed the SYFPEITHI scoring system to identify epitopes on HBV core antigen (HBcAg) for the construction of human leukocyte antigen class II tetramers to measure HBcAg-specific Treg frequencies (Tregf). Upregulation of Treg gene profiling accompanied by increased HBcAg-specific Tregf was detected in AE patients with sustained remission (SR) to anti-HBV therapy. Depletion of Tregs from peripheral blood mononuclear cells enhanced proliferation to HBcAg. HBcAg-specific Treg clones inhibited the killing capacity of cytotoxic T lymphocyte clones in an antigen-independent manner. A greater posttherapy increase in HBcAg-specific Tregf correlated with a higher SR rate to anti-HBV therapy. These results suggest that HBcAg-specific Tregs function as suppressor effectors and confer SR to anti-HBV therapy.
- Published
- 2010