Analysis of the CD8-positive T cell response in Japanese patients with chronic hepatitis C using HLA-A*2402 peptide tetramers
Article first published online: 4 MAR 2003
Copyright © 2003 Wiley-Liss, Inc.
Journal of Medical Virology
Volume 70, Issue 1, pages 51–61, May 2003
How to Cite
Nakamoto, Y., Kaneko, S., Takizawa, H., Kikumoto, Y., Takano, M., Himeda, Y. and Kobayashi, K. (2003), Analysis of the CD8-positive T cell response in Japanese patients with chronic hepatitis C using HLA-A*2402 peptide tetramers. J. Med. Virol., 70: 51–61. doi: 10.1002/jmv.10349
- Issue published online: 4 MAR 2003
- Article first published online: 4 MAR 2003
- Manuscript Accepted: 2 DEC 2002
- hepatitis C virus;
- peripheral blood mononuclear cells; HLA-A24;
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. J. Med. Virol. 70: 51–61, 2003. © 2003 Wiley-Liss, Inc.