Accumulation of dysfunctional effector CD8+ T cells in the liver of patients with chronic HCV infection
Accumulation of dysfunctional effector CD8+ T cells in the liver of patients with chronic HCV infection
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DOI：
10.1016/j.jhep.2005.10.023
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发表时间：
2006-03-01
影响因子：
25.7
通讯作者：
Oliva, A
中科院分区：
文献类型：
--
作者：
Nisii, C;Tempestilli, M;Oliva, A
背景/目的：丙型肝炎病毒（HCV）引起慢性感染，可导致纤维化和癌。由细胞毒性T淋巴细胞（CTL）介导的免疫应答可能参与病毒清除或持续存在，因此决定疾病的进程。方法：从32名HCV慢性感染患者获得肝内和外周血CD 8 + T细胞，并通过流式细胞术分析分化的表面标志物、IFN γ和TNF α产生、脱粒能力和穿孔素含量，CD 3触发后。结果进行了比较，从13例非病毒性肝病。结果：HCV感染患者的肝内CD 8 +T细胞，尽管其表型的前终末和终末分化的效应（CCR 7-CD 45 RA-/+），是不良反应的T细胞受体（TCR）介导的刺激相比，未感染的受试者。这种缺陷与纤维化的严重程度，是更明显的ALT < 1.5 X N than with ALT >1.5 × N U/ml的患者，并不明显后，丝裂原stimulation.Conclusions：本研究描述了低反应性CD 8 + T细胞在慢性HCV感染患者的肝脏中的积累。了解这种损害的机制可能有助于设计HCV治疗的创新策略。(c)2005年欧洲肝脏研究协会。Elsevier B. V.出版，保留所有权利。
Background/Aims: Hepatitis C virus (HCV) causes a chronic infection that can lead to fibrosis and carcinoma. Immune responses mediated by cytotoxic T lymphocytes (CTLs) could be involved in viral clearance or persistence, and therefore in determining the course of the disease.Methods: Intrahepatic and peripheral blood CD8 + T cells were obtained from 32 HCV-chronically infected patients and analysed by flow-cytometry for surface markers of differentiation, IFN gamma and TNF alpha production, degranulation capacity and perforin content, after CD3 triggering. Results were compared with those obtained from 13 patients with a non-viral liver disease.Results: Intrahepatic CD8+T cells of HCV-infected patients, despite their phenotype of pre-terminally and terminally differentiated effectors (CCR7-CD45RA-/+), are poorly responsive to T cell receptor (TCR)-mediated stimulation compared with those obtained from uninfected subjects. This defect correlates with the severity of fibrosis, is more pronounced in patients with ALT < 1.5 X N than with ALT > 1.5 X N U/ml, and is not evident after mitogen stimulation.Conclusions: The present study describes the accumulation of hypo-responsive CD8 + T cells in the liver of patients with chronic HCV infection. Understanding the mechanisms underlying this impairment may be helpful in the design of innovative strategies for HCV treatment. (c) 2005 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.