title: Analysis of the CD8-positive T cell response in Japanese patients with chronic hepatitis C using HLA-A*2402 peptide tetramers.
abstract: Hepatitis C virus (HCV)-specific CD8+ cytotoxic T lymphocytes (CTL) contribute to viral clearance in acute, self-limited hepatitis C as well as to liver cell injury in the more frequent cases with chronic hepatitis C. Although HLA class I-peptide tetramers have been used to detect circulating HCV epitope-specific CTL with a high sensitivity and specificity, this technique has been targeted exclusively to the most frequent HLA haplotypes in the Caucasian population and the large number of HCV-infected Asian patients, most of whom are HLA-A24 positive, have not been studied. The current study determines the frequency, phenotype, and clinical significance of HCV-specific CD8(+) T lymphocytes with five different HLA-A*2402 tetramers in 43 HCV infected Japanese patients and 32 controls. Overall, tetramer(+) cells were detected in the blood of 33 of 43 patients at frequencies of 0.064-0.75% CD8(+)CD4(-)CD14(-)CD19(-) T lymphocytes. Interestingly, although the T cell response was always targeted multispecifically against epitopes in different HCV proteins, the relative frequency of cells stained with individual tetramers differed between patients. Furthermore, tetramer(+)CD8(+) T lymphocytes were highly activated, but the phenotypes of different tetramer(+) cells varied in each patient. In conclusion, HLA-A24 restricted, HCV-specific CD8(+) T lymphocytes are found at similar frequencies in Asian patients as HLA-A2 restricted, HCV-specific CD8(+) T lymphocytes in Caucasian patients. Differences in the frequency and activation status of individual tetramer(+) cell populations suggest that CD8(+) T lymphocytes with different HCV epitope specificity may mediate differential pathogenetic effects in chronic hepatitis C.
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, Kanazawa University, Kanazawa, Japan.
authors.forename: Yasunari
authors.initials: Y
authors.lastname: Nakamoto
authors.forename: Shuichi
authors.initials: S
authors.lastname: Kaneko
authors.forename: Hisao
authors.initials: H
authors.lastname: Takizawa
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Kikumoto
authors.forename: Masaaki
authors.initials: M
authors.lastname: Takano
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Himeda
authors.forename: Kenichi
authors.initials: K
authors.lastname: Kobayashi
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D018929:Cell Culture Techniques; D000939:Epitopes / Q000276:immunology; D005434:Flow Cytometry; D015234:HLA-A Antigens / Q000276:immunology*; D059871:HLA-A24 Antigen; D016174:Hepacivirus / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000276:immunology*; D006801:Humans; D007564:Japan; D010446:Peptide Fragments / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000821:virology
chemical_list: D000939:Epitopes; D015234:HLA-A Antigens; C438506:HLA-A*24:02 antigen; D059871:HLA-A24 Antigen; D010446:Peptide Fragments