NK cells lacking FcεRIγ are associated with reduced liver damage in chronic hepatitis C virus infection

• Published in: European journal of immunology 2016-04, Vol.46 (4), p.1020-1029
• Main Authors: Oh, Jun S., Ali, Alaa K., Kim, Sungjin, Corsi, Daniel J., Cooper, Curtis L., Lee, Seung‐Hwan
• Format: Article
• Language: English
• Subjects: ADCC ⋅ Cytomegalovirus (CMV) ⋅ Hepatitis C virus (HCV) ⋅ Liver enzymes ⋅ Liver fibrosis ⋅ Natural killer (NK) cells; Adult; Antibodies, Viral - immunology; Antibody-Dependent Cell Cytotoxicity - genetics; Antibody-Dependent Cell Cytotoxicity - immunology; CD56 Antigen - genetics; Cytomegalovirus; Cytomegalovirus Infections - immunology; Cytomegalovirus Infections - virology; Cytotoxicity, Immunologic - immunology; Female; Hepacivirus - immunology; Hepatitis C virus; Hepatitis C, Chronic - immunology; Hepatitis C, Chronic - virology; Human cytomegalovirus; Humans; Killer Cells, Natural - immunology; Liver - pathology; Liver - virology; Male; Middle Aged; Receptors, IgE - genetics; Receptors, IgE - immunology
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.201546009

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 CD56neg 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. Our study identified that the presence of CMV‐driven NK cells is associated with reduced liver damage in chronic HCV patients. The results support a unique symbiotic interaction between CMV and NK cells leading to favorable clinical outcomes, prompting further studies to investigate impact of the NK cells on other persistent diseases.