Quantitative analysis of the peripheral blood cytotoxic T lymphocyte response in patients with chronic hepatitis C virus infection
Quantitative analysis of the peripheral blood cytotoxic T lymphocyte response in patients with chronic hepatitis C virus infection
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DOI：
10.1172/jci118931
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发表时间：
1996-09-15
影响因子：
15.9
通讯作者：
Chisari, FV
中科院分区：
文献类型：
--
作者：
Rehermann, B;Chang, KM;Chisari, FV
慢性丙型肝炎病毒（HCV）特异性细胞毒性T淋巴细胞（CTL）存在于慢性感染患者的外周血和肝脏中。目前的研究是为了研究CTL反应强度、肝脏疾病严重程度和病毒载量之间的关系。结果可以总结如下：首先，使用CTL前体频率（CTLpf）分析来定量外周血CTL反应，慢性感染患者对一组明确定义的HCV表位的敏感性低于对流感基质蛋白中的表位的敏感性。其次，在大多数患者的横断面基础上，hcv特异性CTLpf与疾病活动性或病毒载量无关，尽管它确实在3名患者中伴随着肝脏疾病的急剧增加。最后，干扰素治疗并没有增强这些患者对HCV表位的CTLpf，表明其抗病毒作用与CTL反应无关。由于血液中HCV特异性CTLpf实际上相当低，CTL可能导致这些患者持续的肝脏疾病，而数量不足以破坏所有感染的肝细胞，从而促进HCV持续存在并导致慢性肝病。
Hepatitis C virus (HCV)-specific cytotoxic T lymphocytes (CTL) are present in the peripheral blood and liver of chronically infected patients. The current study was performed to study the relationship between the strength of the CTL response, liver disease severity, and viral load. The results may be summarized as follows: first, using CTL precursor frequency (CTLpf) analysis to quantitate the peripheral blood CTL response, chronically infected patients were less strongly sensitized to a panel of well-defined HCV epitopes than they were to an epitope within the influenza matrix protein. Second, HCV-specific CTLpf did not correlate with disease activity or viral load in the majority of patients on a cross-sectional basis, although it did increase in three patients concomitant with sharp increases in liver disease. Finally, interferon therapy did not enhance the CTLpf against the HCV epitopes studied in these patients, indicating that its antiviral effect is independent of the CTL response. Since the HCV-specific CTLpf in the blood is actually quite low, the CTL may contribute to ongoing liver disease in these patients while being quantitatively inadequate to destroy all of the infected hepatocytes, thereby facilitating HCV persistence and contributing to chronic liver disease.