Resolution of chronic hepatitis B and anti-HBs seroconversion in humans by adoptive transfer of immunity to hepatitis B core antigen |
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Authors: | Lau George K K Suri Deepak Liang Raymond Rigopoulou Eirini I Thomas Mark G Mullerova Ivana Nanji Amin Yuen Siu-Tsan Williams Roger Naoumov Nikolai V |
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Institution: | Institute of Hepatology, University College London, London, England. |
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Abstract: | 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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Keywords: | BMT bone marrow transplantation CTL cytotoxic T lymphocytes FITC fluorescein isothiocyanate IFN interferon PBMC peripheral blood mononuclear cell PCR polymerase chain reaction PE phycoerythrin rHBcAg recombinant hepatitis B core antigen rHBsAg recombinant hepatitis B surface antigen SFC spot-forming cell SI stimulation index |
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