Storr Liver Centre, The Westmead Institute for Medical Research, University of Sydney, Westmead, New South Wales, Australia.
Faculty of Medicine, Pelita Harapan University, Tangerang, Indonesia.
J Infect Dis. 2021 Apr 8;223(7):1183-1195. doi: 10.1093/infdis/jiaa492.
Direct acting antiviral therapies rapidly clear chronic hepatitis C virus (HCV) infection and restore natural killer (NK) cell function. We investigated NK-cell memory formation following HCV clearance by examining NK-cell phenotype and responses from control and chronic HCV patients before and after therapy following sustained virologic response at 12 weeks post therapy (SVR12). NK-cell phenotype at SVR12 differed significantly from paired pretreatment samples, with an increase in maturation markers CD16, CD57, and KLRG1. HCV patients possessed stronger cytotoxic responses against HCV-infected cells as compared to healthy controls; a response that further increased following SVR12. The antigen-specific response was mediated by KLRG1+ NK cells, as demonstrated by increased degranulation and proliferation in response to HCV antigen only. Our data suggest that KLRG1+ HCV-specific memory NK cells develop following viral infection, providing insight into their role in HCV clearance and relevance with regard to vaccine design.
直接作用抗病毒疗法可迅速清除慢性丙型肝炎病毒（HCV）感染并恢复自然杀伤（NK）细胞功能。我们通过检查治疗后持续病毒学应答 12 周（SVR12）时的对照和慢性 HCV 患者的 NK 细胞表型和反应，研究了 HCV 清除后 NK 细胞记忆的形成。SVR12 时的 NK 细胞表型与配对的预处理样本明显不同，成熟标志物 CD16、CD57 和 KLRG1 增加。与健康对照相比，HCV 患者对 HCV 感染细胞具有更强的细胞毒性反应；这种反应在 SVR12 后进一步增加。抗原特异性反应由 KLRG1+NK 细胞介导，这一点通过仅对 HCV 抗原的脱颗粒和增殖反应增加得到证明。我们的数据表明，KLRG1+HCV 特异性记忆 NK 细胞在病毒感染后会产生，这为它们在 HCV 清除中的作用以及与疫苗设计的相关性提供了深入了解。
