title: High frequency of circulating HBcAg-specific CD8 T cells in hepatitis B infection: a flow cytometric analysis.
abstract: Viral antigen-specific T cells are important for virus elimination. We studied the hepatitis B virus (HBV)-specific T cell response using flow cytometry. Three phases of HBV infection were studied: Group A, HBeAg (+) chronic hepatitis; Group B, HBeAb (+) HBV carrier after seroconversion; and Group C, HBsAb (+) phase. Peripheral T cells were incubated with recombinant HB core antigen (HBcAg), and intracytoplasmic cytokines were analysed by flow cytometry. HBcAg-specific CD4 and CD8 T cells were identified in all three groups and the number of IFN-gamma-positive T cells was greater than TNF-alpha-positive T cells. The frequency of IFN-gamma-positive CD4 and CD8 T cells was highest in Group C, compared with Groups A and B. No significant difference in the HBcAg-specific T cell response was observed between Group A and Group B. The HBcAg-specific CD8 T cell response was diminished by CD4 depletion, addition of antibody against human leucocyte antigen (HLA) class I, class II or CD40L. Cytokine-positive CD8 T cells without HBcAg stimulation were present at a high frequency (7 of 13 cases) in Group B, but were rare in other groups. HBcAg-specific T cells can be detected at high frequency by a sensitive flow cytometric analysis, and these cells are important for controlling HBV replication.
authors.affiliation: First Department of Internal Medicine, Okayama University Medical School, Okayama, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Matsumura
authors.forename: K
authors.initials: K
authors.lastname: Yamamoto
authors.forename: N
authors.initials: N
authors.lastname: Shimada
authors.forename: N
authors.initials: N
authors.lastname: Okano
authors.forename: R
authors.initials: R
authors.lastname: Okamoto
authors.forename: T
authors.initials: T
authors.lastname: Suzuki
authors.forename: T
authors.initials: T
authors.lastname: Hakoda
authors.forename: M
authors.initials: M
authors.lastname: Mizuno
authors.forename: T
authors.initials: T
authors.lastname: Higashi
authors.forename: T
authors.initials: T
authors.lastname: Tsuji
mesh_terms: D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005434:Flow Cytometry / Q000379:methods; D006509:Hepatitis B / Q000097:blood / Q000276:immunology*; D006512:Hepatitis B Core Antigens / Q000097:blood / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology; D015203:Reproducibility of Results; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D006512:Hepatitis B Core Antigens; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma