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 haplo-types 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. © 2003 Wiley-Liss, Inc.