title: Interferon-gamma is produced by CD8 T cells in response to HLA-A24-restricted hepatitis C virus epitopes after sustained virus loss.
abstract: Differences in cytotoxic T lymphocyte activity in hepatitis C virus infection may account for the outcome of interferon monotherapy. To investigate this hypothesis, we analysed the response of peripheral CD8(+) T cells that recognized epitopes presented by HLA-A*2402. We synthesized HLA/beta2-microglobulin/peptide complexes using two epitopes. Production of interferon-gamma by CD8(+) T cells in response to plastic-bound monomeric HLA/peptide complex was observed frequently in sustained virus responders (SVR) (n = 13) against all the peptides, NS31296-1304 (the percentage of responding patients, 61.5%) and core 129-137 (53.8%), while no interferon-gamma production was observed in non-responders (NR) (n = 13) for any of the peptides. Tetramer-staining showed the presence of CD8(+) T cells specific for all the peptides except NS31296-1304 in two SVR at the end of interferon monotherapy, although hardly any such cells were found in four NR. Specific killing was observed against peptides NS31296-1304 (3/4) and core 129-137 (1/4) in sustained responders but none in non-responders. These results suggest that the responses of cytotoxic T lymphocytes (CTLs) were induced during interferon therapy in these patients and that interferon-gamma production by CD8(+) T lymphocytes against HCV NS31296-1304 and core 129-137 are well maintained in patients with SVR compared with those with NR. These findings emphasize the importance of the CD8(+) T cell response in controlling HCV infection.
authors.affiliation: Tohoku University School of Health Sciences and Comprehensive Research and Education Center for Planning of Drug Development and Clinical Evaluation, Sendai, Japan. kobakoju@mail.tains.tohoku.ac.jp
authors.forename: K
authors.initials: K
authors.lastname: Kobayashi
authors.forename: M
authors.initials: M
authors.lastname: Ishii
authors.forename: M
authors.initials: M
authors.lastname: Shiina
authors.forename: Y
authors.initials: Y
authors.lastname: Ueno
authors.forename: Y
authors.initials: Y
authors.lastname: Kondo
authors.forename: A
authors.initials: A
authors.lastname: Kanno
authors.forename: Y
authors.initials: Y
authors.lastname: Miyazaki
authors.forename: T
authors.initials: T
authors.lastname: Yamamoto
authors.forename: T
authors.initials: T
authors.lastname: Kobayashi
authors.forename: H
authors.initials: H
authors.lastname: Niitsuma
authors.forename: Y
authors.initials: Y
authors.lastname: Kikumoto
authors.forename: H
authors.initials: H
authors.lastname: Takizawa
authors.forename: T
authors.initials: T
authors.lastname: Shimosegawa
mesh_terms: D000328:Adult; D000368:Aged; D000956:Antigens, Viral / Q000276:immunology; D000998:Antiviral Agents / Q000627:therapeutic use; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D015234:HLA-A Antigens / Q000276:immunology*; D059871:HLA-A24 Antigen; D016174:Hepacivirus / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000276:immunology* / Q000628:therapy; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D007371:Interferon-gamma / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D000956:Antigens, Viral; D000998:Antiviral Agents; D018984:Epitopes, T-Lymphocyte; D015234:HLA-A Antigens; D059871:HLA-A24 Antigen; D016898:Interferon-alpha; D007371:Interferon-gamma