Cimini E, Bordoni V, Sacchi A, Visco-Comandini U, Montalbano M, Taibi C, Casetti R, Lalle E, D'Offizi G, Capobianchi M R, Agrati C
Laboratory of Cellular Immunology and Pharmacology, INMI-IRCCS "L. Spallanzani", Via Portuense 292, 00149, Rome, Italy.
Clinical Department, INMI-IRCCS "L. Spallanzani", Via Portuense 292, 00149, Rome, Italy.
Virus Res. 2018 Jan 2;243:31-35. doi: 10.1016/j.virusres.2017.10.008. Epub 2017 Oct 10.
Hepatitis C virus (HCV) persistence results from inefficiencies of both innate and adaptive immune responses to eradicate the infection. A functional impairment of circulating Vγ9Vδ2 T-cells was described but few data are available on Vγ9Vδ2 T-cells in the liver that, however, represents the battlefield in the HCV/host interaction. Aim of this work was to compare circulating and intrahepatic Vγ9Vδ2 T-cells in chronic HCV-infected patients (HCV) and in HCV-negative (HCV) subjects. Phenotypic and functional analysis was performed by flow cytometry. Anti-HCV activity was analyzed by using an in vitro autologous liver culture system. Independently from HCV infection, the liver was enriched of Vγ9Vδ2 T-cells expressing an effector/activated phenotype. In contrast, an enrichment of PD-1 expressing Vγ9Vδ2 T-cells was observed both in the peripheral blood and in the liver of HCV patients, probably due to a persistent antigenic stimulation. Moreover, a lower frequency of IFN-γ producing Vγ9Vδ2 T-cells was observed in the liver of HCV patients, suggesting a functional impairment in the cytokine production in HCV liver. Despite this hypo-responsiveness, intrahepatic Vγ9Vδ2 T-cells are able to exert an anti-HCV activity after specific stimulation. Altogether, our data show that HCV infection induced a dysregulation of intrahepatic Vγ9Vδ2 T cells that maintain their anti-HCV activity after specific stimulation. A study aimed to evaluate the mechanisms of the antiviral activity may be useful to identify new pathways able to improve Vγ9Vδ2 T-cells intrahepatic function during HCV infection.
丙型肝炎病毒（HCV）持续存在是由于先天性和适应性免疫反应在根除感染方面效率低下所致。已有文献报道循环Vγ9Vδ2 T细胞存在功能障碍，但关于肝脏中Vγ9Vδ2 T细胞的数据却很少，然而肝脏却是HCV与宿主相互作用的战场。本研究的目的是比较慢性HCV感染患者（HCV）和HCV阴性（HCV）受试者的循环和肝内Vγ9Vδ2 T细胞。通过流式细胞术进行表型和功能分析。使用体外自体肝脏培养系统分析抗HCV活性。与HCV感染无关，肝脏中富含表达效应/活化表型的Vγ9Vδ2 T细胞。相反，在HCV患者的外周血和肝脏中均观察到表达PD-1的Vγ9Vδ2 T细胞增多，这可能是由于持续的抗原刺激所致。此外，在HCV患者的肝脏中观察到产生IFN-γ的Vγ9Vδ2 T细胞频率较低，这表明HCV感染的肝脏中细胞因子产生存在功能障碍。尽管存在这种低反应性，但肝内Vγ9Vδ2 T细胞在特异性刺激后仍能够发挥抗HCV活性。总之，我们的数据表明，HCV感染导致肝内Vγ9Vδ2 T细胞失调，这些细胞在特异性刺激后仍保持其抗HCV活性。一项旨在评估抗病毒活性机制的研究可能有助于确定在HCV感染期间能够改善肝内Vγ9Vδ2 T细胞功能的新途径。
