Hepatitis B virus (HBV) core antigen-specific regulatory T cells confer sustained remission to anti-HBV therapy in chronic hepatitis B with acute exacerbation.

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.

• Authors: Lok-Beng Koay, I-Che Feng, Ming-Jen Sheu, Hsing-Tao Kuo, Chin-Yih Lin, Jyh-Jou Chen, Shih-Ling Wang, Ling-Yu Tang, Sun-Lung Tsai
• Journal: Human immunology (Hum Immunol) Vol. 72 Issue 9 Pg. 687-98 (Sep 2011) ISSN: 1879-1166 [Electronic] United States
• PMID: 21215784 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011. Published by Elsevier Inc.

Chemical References

• Antiviral Agents
• Epitopes
• FOXP3 protein, human
• Forkhead Transcription Factors
• Hepatitis B Core Antigens
• Histocompatibility Antigens Class II

Topics

• Antiviral Agents (therapeutic use)
• Cell Proliferation
• Cytotoxicity, Immunologic
• Epitope Mapping
• Epitopes (metabolism)
• Forkhead Transcription Factors (biosynthesis)
• Hepatitis B Core Antigens (immunology, metabolism)
• Hepatitis B virus (immunology, pathogenicity)
• Hepatitis B, Chronic (drug therapy, immunology, physiopathology)
• Histocompatibility Antigens Class II (metabolism)
• Humans
• Immunosuppression Therapy
• Liver Failure
• Protein Binding
• Remission Induction
• T-Cell Antigen Receptor Specificity
• T-Lymphocyte Subsets (immunology, metabolism, pathology, virology)
• T-Lymphocytes, Regulatory (immunology, metabolism, pathology, virology)