title: Resolution of chronic hepatitis B and anti-HBs seroconversion in humans by adoptive transfer of immunity to hepatitis B core antigen.
abstract: OBJECTIVE
  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.
authors.affiliation: Institute of Hepatology, University College London, London, England.
authors.forename: George K K
authors.initials: GK
authors.lastname: Lau
authors.forename: Deepak
authors.initials: D
authors.lastname: Suri
authors.forename: Raymond
authors.initials: R
authors.lastname: Liang
authors.forename: Eirini I
authors.initials: EI
authors.lastname: Rigopoulou
authors.forename: Mark G
authors.initials: MG
authors.lastname: Thomas
authors.forename: Ivana
authors.initials: I
authors.lastname: Mullerova
authors.forename: Amin
authors.initials: A
authors.lastname: Nanji
authors.forename: Siu-Tsan
authors.initials: ST
authors.lastname: Yuen
authors.forename: Roger
authors.initials: R
authors.lastname: Williams
authors.forename: Nikolai V
authors.initials: NV
authors.lastname: Naoumov
mesh_terms: D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000821:virology; D002455:Cell Division / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006510:Hepatitis B Antibodies / Q000097:blood; D006512:Hepatitis B Core Antigens / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000276:immunology* / Q000628:therapy*; D006801:Humans; D016219:Immunotherapy, Adoptive; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged
chemical_list: D006510:Hepatitis B Antibodies; D006512:Hepatitis B Core Antigens