Wong D K, Dudley D D, Afdhal N H, Dienstag J, Rice C M, Wang L, Houghton M, Walker B D, Koziel M J
Infectious Diseases Unit, Massachusetts General Hospital, Boston 02114, USA.
J Immunol. 1998 Feb 1;160(3):1479-88.
Hepatitis C virus (HCV)-specific CTL have been found within the inflammatory infiltrate of the liver of chronically infected individuals, but the breadth and specificity of the CTL response in relation to viral load are less well characterized. In this study, we analyzed the intrahepatic CTL response in liver biopsy specimens from 44 chronically infected subjects. Liver-infiltrating lymphocytes were expanded polyclonally in bulk cultures, and multiple clones were derived by limiting dilution. HCV-specific CTL responses directed at genotype 1a structural proteins were assessed in all subjects, and 22 subjects were tested more comprehensively using vectors expressing all structural and nonstructural HCV Ags. CTL responses were further characterized to determine the HLA restriction and optimal epitopes recognized. In those persons screened for recognition of all HCV Ags, HLA class I-restricted CTL were detected in 45%. Nineteen different CTL epitopes were identified, which were distributed throughout the genome; only one epitope was targeted by more than one person. In those persons with CTL responses, the breadth of response ranged from one to five epitopes. There was no correlation between the presence of a detectable CTL response and viral load. These results indicate considerable heterogeneity in detectable HCV-specific CTL responses in chronically infected persons. The mechanisms by which HCV persists during chronic infection remain to be clarified.
在慢性感染个体的肝脏炎性浸润物中已发现丙型肝炎病毒（HCV）特异性CTL，但CTL反应相对于病毒载量的广度和特异性仍未得到充分表征。在本研究中，我们分析了44例慢性感染受试者肝脏活检标本中的肝内CTL反应。肝浸润淋巴细胞在大量培养物中多克隆扩增，并通过有限稀释获得多个克隆。在所有受试者中评估了针对1a基因型结构蛋白的HCV特异性CTL反应，并使用表达所有HCV结构和非结构抗原的载体对22例受试者进行了更全面的检测。进一步表征CTL反应以确定HLA限制和识别的最佳表位。在那些筛选出对所有HCV抗原均有识别反应的人中，45%检测到HLA I类限制性CTL。鉴定出19种不同的CTL表位，它们分布在整个基因组中；只有一个表位被不止一人靶向。在那些有CTL反应的人中，反应广度为1至5个表位。可检测到的CTL反应的存在与病毒载量之间没有相关性。这些结果表明，慢性感染个体中可检测到的HCV特异性CTL反应存在相当大的异质性。HCV在慢性感染期间持续存在的机制仍有待阐明。
