Resolution of chronic hepatitis B and anti-HBs seroconversion in humans by adoptive transfer of immunity to hepatitis B core antigen

被引:168
作者
Lau, GKK
Suri, D
Liang, R
Rigopoulou, EI
Thomas, MG
Mullerova, I
Nanji, A
Yuen, ST
Williams, R
Naoumov, NV
机构
[1] UCL, Inst Hepatol, London WC1E 6HX, England
[2] UCL, Dept Biol, London WC1E 6HX, England
[3] Queen Marys Hosp, Dept Med, Hong Kong, Hong Kong, Peoples R China
[4] Queen Marys Hosp, Dept Pathol, Hong Kong, Hong Kong, Peoples R China
关键词
D O I
10.1053/gast.2002.31887
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background & Aims: Impaired T-cell reactivity is believed to be the dominant cause of chronic hepatitis B virus (HBV) infection. We characterized HBV-specific T-cell responses in chronic hepatitis B surface antigen carriers who received bone marrow from HLA-identical donors with natural immunity to HBV and seroconverted to antibody to hepatitis B surface antigen. Methods: T-cell reactivity to HBV antigens and peptides was assessed in a proliferation assay, the frequency of HBV core- and surface-specific T cells was quantified directly by ELISPOT assays, and T-cell subsets were analyzed by flow cytometry. Results: CD4(+) T-cell reactivity to HBV core was common in bone marrow donors and the corresponding recipients after hepatitis B surface antigen clearance, whereas none reacted to surface, pre-S1 or pre-S2 antigens. Furthermore, CD4(+) T cells from donor/recipient pairs recognized similar epitopes on hepatitis B core antigen; using polymerase chain reaction for the Y chromosome, the recipients' CD4(+) T lymphocytes were confirmed to be of donor origin. The frequency of core-specific CD4(+) and CD8(+) T cells was several-fold higher than those specific for surface antigen. Conclusions: This study provides the first evidence in humans that transfer of hepatitis B core antigen-reactive T cells is associated with resolution of chronic HBV infection. Therapeutic immunization with HBV core gene or protein deserves further investigation in patients with chronic hepatitis B.
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页码:614 / 624
页数:11
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