Longitudinal analysis of peripheral and intrahepatic NK cells in chronic HCV patients during antiviral therapy
Longitudinal analysis of peripheral and intrahepatic NK cells in chronic HCV patients during antiviral therapy
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DOI：
10.1016/j.antiviral.2015.09.006
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发表时间：
2015-11-01
影响因子：
7.6
通讯作者：
Boonstra, Andre
中科院分区：
文献类型：
--
作者：
Spaan, Michelle;van Oord, Gertine W.;Boonstra, Andre
简介：强免疫应答是清除HCV感染的必要条件。NK细胞是能够抑制HCV在受感染肝细胞中复制的特化细胞。先前的研究已经将HCV的治疗结果与NK细胞上各种标志物的表达相关联。然而，治疗期间病毒载量减少对NK细胞功能的影响在很大程度上仍然未知，特别是在肝脏中。因此，我们研究了NK细胞表型和效应功能在外周和肝内隔室在抗病毒治疗过程中的慢性HCVpatient.Methods：慢性HCV患者进行了治疗24或48周的三联疗法由特拉匹韦，聚乙二醇干扰素-α和利巴韦林。分别于治疗开始时、治疗后6 h、1周、12周采集血液标本和肝脏细针穿刺活检标本。流式细胞术进行不同的标志物（NKG 2A，NMG 2D，NMp 46，和CD 69）的表达。结果：我们的研究结果表明，在慢性丙型肝炎患者的肝脏相比，血液中的NK细胞的高度活化的表型。三联治疗开始后6小时，与基线相比，在肝脏中未观察到肝内NK细胞活化。在三联疗法开始后1周，血液中具有活化受体NKp 46的NK细胞的频率增加，而在第12周，抑制性受体NKG 2A的频率增加。结论：以IFN为基础的慢性HCV治疗对外周血NK细胞表型的影响大于对肝脏NK细胞表型的影响。(C)2015 Elsevier B. V.版权所有。
Introduction: A strong immune response is integral to the clearance of HCV infection. NK cells are specialized cells that are able to inhibit replication of HCV in infected hepatocytes. Previous studies have correlated therapy Outcome in HCV to the expression of various markers on NK cells. However, the effect of viral load reduction on NK cell function during therapy is still largely unknown, particularly in the liver. Therefore we investigated NK cell phenotype and effector function in both the peripheral and intrahepatic compartments during the course of antiviral therapy in chronic HCV patients.Methods: Chronic HCV patients were treated for 24 or 48 weeks with triple therapy consisting of telaprevir, pegIFN-alpha and ribavirin. Blood and fine needle aspiration (FNA) biopsies of the liver were collected at start and 6 h, 1 week and 12 weeks during therapy. Flowcytometry was performed for expression of different markers (NKG2A, NMG2D, NMp46, and CD69).Results: Our results demonstrate a highly activated phenotype of NK cells in liver compared to blood in chronic HCV patients. Six hours after start of triple therapy, no activation of intrahepatic NK cells was observed in the liver as compared to baseline. At 1 week after start of triple therapy, the frequency of NK cells with the activating receptor NKp46 was increased in blood, whereas at week 12, the frequencies of the inhibitory receptor NKG2A was increased. No alterations were observed during therapy in liver NK cell phenotype.Conclusion: IFN-based therapy for chronic HCV affects NK cell phenotype in peripheral blood more than in the liver. (C) 2015 Elsevier B.V. All rights reserved.