Analysis of the CD8‐positive T cell response in Japanese patients with chronic hepatitis C using HLA‐A*2402 peptide tetramers
Analysis of the CD8‐positive T cell response in Japanese patients with chronic hepatitis C using HLA‐A*2402 peptide tetramers
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DOI：
10.1002/jmv.10349
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发表时间：
2003-05
影响因子：
12.7
通讯作者：
Y. Nakamoto;S. Kaneko;H. Takizawa;Y. Kikumoto;M. Takano;Yoshiko Himeda;Kenichi Kobayashi
中科院分区：
文献类型：
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作者：
Y. Nakamoto;S. Kaneko;H. Takizawa;Y. Kikumoto;M. Takano;Yoshiko Himeda;Kenichi Kobayashi
丙型肝炎病毒（HCV）特异性CD 8+细胞毒性T淋巴细胞（CTL）有助于急性自限性丙型肝炎的病毒清除，以及更常见的慢性丙型肝炎病例的肝细胞损伤。尽管HLA I类肽四聚体已被用于检测循环HCV表位特异性CTL，具有高灵敏度和特异性，但该技术仅针对高加索人群中最常见的HLA单倍型，尚未研究大量HCV感染的亚洲患者，其中大多数为HLA-A24阳性。目前的研究确定了43名HCV感染的日本患者和32名对照者中具有5种不同HLA-A *2402四聚体的HCV特异性CD 8 + T淋巴细胞的频率，表型和临床意义。总体而言，在43例患者中的33例血液中检测到四聚体+细胞，频率为0.064-0.75% CD 8 + CD 4 − CD 14 − CD 19 − T淋巴细胞。有趣的是，尽管T细胞反应总是针对不同HCV蛋白中的表位进行多特异性靶向，但用单个四聚体染色的细胞的相对频率在患者之间不同。此外，四聚体+CD 8 + T淋巴细胞高度活化，但不同的四聚体+细胞的表型在每个患者中不同。总之，亚洲患者中HLA-A24限制性HCV特异性CD 8 + T淋巴细胞的频率与高加索患者中HLA-A2限制性HCV特异性CD 8 + T淋巴细胞的频率相似。单个四聚体+细胞群的频率和活化状态的差异表明，具有不同HCV表位特异性的CD 8 + T淋巴细胞可能介导慢性丙型肝炎的不同致病作用。医学病毒学杂志70：51-61，2003.© 2003 Wiley利斯公司
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.