Oh Jun S, Ali Alaa K, Kim Sungjin, Corsi Daniel J, Cooper Curtis L, Lee Seung-Hwan
Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Canada.
Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI, USA.
Eur J Immunol. 2016 Apr;46(4):1020-9. doi: 10.1002/eji.201546009. Epub 2016 Jan 18.
A novel subset of human natural killer (NK) cells, which displays potent and broad antiviral responsiveness in concert with virus-specific antibodies, was recently uncovered in cytomegalovirus (CMV)+ individuals. This NK-cell subset (g-NK) was characterized by a deficiency in the expression of FcεRIγ adaptor protein and the long-lasting memory-like NK-cell phenotype, suggesting a role in chronic infections. This study investigates whether the g-NK-cell subset is associated with the magnitude of liver disease during chronic hepatitis C virus (HCV) infection. Analysis of g-NK-cell proportions and function in the PBMCs of healthy controls and chronic HCV subjects showed that chronic HCV subjects had slightly lower proportions of the g-NK-cell subset having similarly enhanced antibody-dependent cellular cytotoxicity responses compared to conventional NK cells. Notably, among CMV+ chronic HCV patients, lower levels of liver enzymes and fibrosis were found in those possessing g-NK cells. g-NK cells were predominant among the CD56(neg) NK cell population often found in chronic HCV patients, suggesting their involvement in immune response during HCV infection. For the first time, our findings indicate that the presence of the g-NK cells in CMV+ individuals is associated with amelioration of liver disease in chronic HCV infection, suggesting the beneficial roles of g-NK cells during a chronic infection.
最近在巨细胞病毒（CMV）阳性个体中发现了一种新型人类自然杀伤（NK）细胞亚群，该亚群与病毒特异性抗体协同发挥强大且广泛的抗病毒反应。这个NK细胞亚群（g-NK）的特征是缺乏FcεRIγ衔接蛋白的表达以及具有持久的记忆样NK细胞表型，提示其在慢性感染中发挥作用。本研究调查g-NK细胞亚群是否与慢性丙型肝炎病毒（HCV）感染期间的肝脏疾病严重程度相关。对健康对照和慢性HCV患者外周血单个核细胞（PBMC）中g-NK细胞比例和功能的分析表明，与传统NK细胞相比，慢性HCV患者中具有类似增强的抗体依赖性细胞毒性反应的g-NK细胞亚群比例略低。值得注意的是，在CMV阳性的慢性HCV患者中，拥有g-NK细胞的患者肝酶水平和纤维化程度较低。g-NK细胞在慢性HCV患者中常见的CD56阴性NK细胞群体中占主导地位，表明它们参与了HCV感染期间的免疫反应。我们的研究结果首次表明，CMV阳性个体中g-NK细胞的存在与慢性HCV感染中肝脏疾病的改善相关，提示g-NK细胞在慢性感染期间发挥有益作用。
