Resolution of chronic hepatitis B and anti-HBs seroconversion in humans by adoptive transfer of immunity to hepatitis B core antigen.
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.
Lau
George K K
GK
Institute of Hepatology, University College London, London, England.
Suri
Deepak
D
Liang
Raymond
R
Rigopoulou
Eirini I
EI
Thomas
Mark G
MG
Mullerova
Ivana
I
Nanji
Amin
A
Yuen
Siu-Tsan
ST
Williams
Roger
R
Naoumov
Nikolai V
NV
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
D006510:Hepatitis B Antibodies; D006512:Hepatitis B Core Antigens