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目的 阐明丙型肝炎病毒 (HCV)特异性细胞毒性T淋巴细胞 (CTL)在慢性丙型肝炎病毒感染中的作用。方法 用标准铬释放法 (以从患者肝组织或外周血单个核细胞中经选择性克隆扩增后的CD8+细胞为效应细胞 ,经EB病毒转染的自身B淋巴母细胞为靶细胞 ,由能表达HCV1型核心区基因的重组痘苗病毒作为转导载体 )对 62例慢性丙型肝炎患者肝组织及外周血单个核细胞(PBMC)中的HCV特异性CTL活性 (HCV CTL)进行检测 ,8例非HCV感染的肝病患者作为对照。结果 62例慢性丙型肝炎患者中 ,共有 2 8例 ( 4 6.7%)肝组织中检测出HCV CTL活性 ,但HCV CTL在PBMC中未检出。对照组患者肝组织及PBMC中均未检出。 5例非HCV1感染的丙型肝炎患者检测出针对HCV1型表位的HCV CTL。HCV CTL阳性的丙型肝炎患者血清丙氨酸转氨酶 (ALT)、天门冬氨酸转氨酶 (AST)水平及肝组织活动指数均明显高于HCV CTL阴性的患者 ,而其血清HCVRNA水平则显著低于后者 (P <0 .0 1)。结论 1.HCV CTL主要存在于肝组织内 ;2 .存在型交叉性HCV CTL ;3 .HCV CTL活性阳性的患者较HCV CTL活性阴性者具有较高的疾病活动度及较低的病毒血症水平 ;4 .HCV特异性CTL在丙型肝炎的发病机制及疾病控制中起重要作用。
Objective To elucidate the role of hepatitis C virus (HCV) -specific cytotoxic T lymphocytes (CTLs) in chronic hepatitis C virus infection. Methods Standard chromium release assay (with selective clonal expansion of CD8 + cells from patient’s liver or peripheral blood mononuclear cells as effector cells and EB virus-transfected autologous B lymphoblast cells as target cells from HCV-specific CTL activity (HCV CTL) in liver tissue and peripheral blood mononuclear cells (PBMCs) from 62 patients with chronic hepatitis C were detected by using recombinant vaccinia virus expressing core region gene of HCV type 1 as transduction vector. Eight patients Non-HCV-infected liver disease patients served as a control. Results Of the 62 patients with chronic hepatitis C, HCV CTL activity was detected in 28 of 48 (4. 6.7%) liver tissues, but HCV CTL was not detected in PBMC. Control group patients were not detected in liver tissue and PBMC. Five HCV CTLs against the HCV type 1 epitope were detected in 5 non-HCV infected Hepatitis C patients. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and hepatic tissue activity index were significantly higher in patients with HCV CTL-positive hepatitis C than those with negative HCV CTL, while serum HCVRNA levels were significantly lower The latter (P <0. 01). 1.CV CTL mainly exists in liver tissue; 2. Presence-type cross-HCV CTL; 3. Patients with positive HCV CTL activity have higher disease activity and lower viremia than HCV CTL negative patients ; 4.HCV-specific CTL plays an important role in the pathogenesis of hepatitis C and disease control.