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

被引:17
|
作者
Koay, Lok-Beng [1 ]
Feng, I-Che [1 ]
Sheu, Ming-Jen [1 ]
Kuo, Hsing-Tao [1 ]
Lin, Chin-Yih [1 ]
Chen, Jyh-Jou [2 ]
Wang, Shih-Ling [3 ]
Tang, Ling-Yu [3 ]
Tsai, Sun-Lung [1 ,3 ]
机构
[1] Chi Mei Med Ctr, Dept Internal Med, Div Hepatogastroenterol, Tainan, Taiwan
[2] Chi Mei Hosp Liouying, Dept Internal Med, Tainan, Taiwan
[3] Chi Mei Med Ctr, Dept Med Res, Liver Res Unit, Tainan, Taiwan
关键词
Chronic hepatitis B; Gene profiling; HLA-class II tetramer; SYFPEITHI score; Regulatory T-cell clone; LAMIVUDINE THERAPY; IMMUNE-RESPONSE; HEPATOCELLULAR-CARCINOMA; VIRAL-HEPATITIS; NATURAL-HISTORY; SURFACE-ANTIGEN; INFECTION; PEPTIDE; DISEASE; SEROCONVERSION;
D O I
10.1016/j.humimm.2010.11.001
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 CU-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. (C) 2011 Published by Elsevier Inc. on behalf of American Society for Histocompatibility and Immunogenetics.
引用
收藏
页码:687 / 698
页数:12
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