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Resolution of chronic hepatitis B and anti-HBs seroconversion in humans by adoptive transfer of immunity to hepatitis B core antigen.
- Source :
-
Gastroenterology [Gastroenterology] 2002 Mar; Vol. 122 (3), pp. 614-24. - Publication Year :
- 2002
-
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.<br />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.<br />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.<br />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.
- Subjects :
- Adolescent
Adult
CD4-Positive T-Lymphocytes cytology
CD4-Positive T-Lymphocytes immunology
CD4-Positive T-Lymphocytes virology
CD8-Positive T-Lymphocytes cytology
CD8-Positive T-Lymphocytes immunology
CD8-Positive T-Lymphocytes virology
Cell Division immunology
Female
Flow Cytometry
Hepatitis B Antibodies blood
Humans
Lymphocyte Activation immunology
Male
Middle Aged
Bone Marrow Transplantation
Hepatitis B Core Antigens immunology
Hepatitis B, Chronic immunology
Hepatitis B, Chronic therapy
Immunotherapy, Adoptive
Subjects
Details
- Language :
- English
- ISSN :
- 0016-5085
- Volume :
- 122
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Gastroenterology
- Publication Type :
- Academic Journal
- Accession number :
- 11874993
- Full Text :
- https://doi.org/10.1053/gast.2002.31887