Koziel M J, Dudley D, Wong J T, Dienstag J, Houghton M, Ralston R, Walker B D
Infectious Disease Unit, Massachusetts General Hospital, Boston 02114.
J Immunol. 1992 Nov 15;149(10):3339-44.
Hepatitis C virus (HCV) is a major cause of post-transfusion and sporadic hepatitis worldwide, leading to chronic liver disease in at least 50% of infected individuals. The pathogenic mechanisms that result in chronic hepatitis are unknown. Lymphocytes are typically observed within the hepatic parenchyma, but the functional characteristics of these cells have not been defined. In this study, liver-infiltrating lymphocytes from two subjects with chronic HCV hepatitis were cloned at limiting dilution and tested for HCV-specific cytolytic activity using autologous target cells infected with vaccinia viruses expressing recombinant HCV Ag or sensitized with synthetic HCV peptides. In both subjects, HCV-specific, HLA class I-restricted CTL were identified that recognized epitopes in variable regions of either the envelope or nonstructural proteins. These results demonstrate the presence of HCV-specific CTL at the site of tissue damage in persons with chronic HCV hepatitis, and provide a means to evaluate the possible pathogenic role of these cells in HCV infection.
丙型肝炎病毒（HCV）是全球输血后肝炎和散发性肝炎的主要病因，至少50%的感染者会发展为慢性肝病。导致慢性肝炎的致病机制尚不清楚。通常在肝实质内可观察到淋巴细胞，但这些细胞的功能特性尚未明确。在本研究中，对两名慢性丙型肝炎患者的肝浸润淋巴细胞进行有限稀释克隆，并使用感染了表达重组HCV抗原的痘苗病毒或用合成HCV肽致敏的自体靶细胞检测其HCV特异性细胞溶解活性。在两名患者中，均鉴定出HCV特异性、HLA I类限制性CTL，它们识别包膜或非结构蛋白可变区的表位。这些结果证明慢性丙型肝炎患者组织损伤部位存在HCV特异性CTL，并提供了一种评估这些细胞在HCV感染中可能致病作用的方法。
