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发表于 2002-4-5 18:16
Gastroenterology
March 2002 . Volume 122 . Number 3
Clinical Research
Resolution of chronic hepatitis B and anti-HBs seroconversion in humans by adoptive transfer of immunity to hepatitis B core antigen
George K. K. Lau*,? Deepak Suri* Raymond Liang?
Eirini I. Rigopoulou* Mark G. Thomas§Ivana Mullerova*
Amin Nanji|| Siu-Tsan Yuen|| Roger Williams* Nikolai V. Naoumov
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.
*Institute of Hepatology and §Department of Biology, University College London, London, England; and Departments of ?Medicine and ||Pathology, Queen Mary Hospital, Hong Kong, China Received May 2, 2001.Accepted November 15, 2001.GASTROENTEROLOGY 2002;122:614-624 Address requests for reprints to:
Nikolai V. Naoumov, M.D., Institute of Hepatology, University College
London, 69-75 Chenies Mews, London WC1E 6HX, England. e-mail:
[email protected] ; fax: (44) 20-7380 0405. Dr. Lau's work at University College London was supported by a fellowship from The Royal Society, United Kingdom. Dr. Mullerova is a recipient of an EASL Training Fellowship.© 2002 by the American Gastroenterological Association 0016-5085/02/$35.00 doi:10.1053/gast.2002.31887
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