title: CD56brightNK IL-7Rα expression negatively associates with HCV level, and IL-7-induced NK function is impaired during HCV and HIV infections.
abstract: Several lines of evidence support the concept that NK cells play an important role in control of hepatitis C virus (HCV) infection via cytokine secretion and cytotoxicity. IL-7 is a homeostatic cytokine with a role in T cell development, activation, proliferation, and cytokine secretion. The IL-7Rα chain [cluster of differentiation (CD)127] is expressed on NK cells, with greatest abundance on the CD56brightCD16dim/-(CD56bright) subset. Here, we measured CD127 expression on CD56bright, CD56dimCD16+(CD56dim), or CD56negCD16+(CD56neg) NK cell subsets of 25 uninfected donors (UD); 34 chronic HCV-infected, treatment-naïve; 25 HIV-infected, virally suppressed on antiretroviral therapy (ART); and 42 HCV-HIV-coinfected subjects on ART. Interestingly, CD127 expression on CD56brightNK cells negatively correlated with HCV plasma levels in HCV monoinfection and HCV-HIV coinfection. IL-7 induced CD69 expression, as well as IFN-γ production, in CD56brightNK cells and also enhanced the IFN-α-induced CD69 expression on these cells. The latter was impaired in HIV infection. Furthermore, IL-7 induced B cell lymphoma 2 (BCL-2) expression and cell cycling of CD56brightNK cells, and this effect was impaired in HCV- and HIV-infected subjects. Whereas IL-7-stimulated CD56brightNK cell degranulation appeared intact in all cohorts, we observed impaired IL-7-activated NK cell cytolytic function in HCV- and HIV-infected subjects. Finally, IL-7-induced phosphorylation of STAT-5 (pSTAT-5) signaling was impaired in NK cells of subjects with chronic viral infection, and this was reversible upon 6 mo of viral suppression with IFN-free HCV therapy. These results implicate that IL-7-dependent NK cell activation and effector function may be other host immune surveillance mechanisms that are impaired in viral infections.
authors.affiliation: Department of Pathology, Cleveland VA Medical Center, Case Western Reserve University, Cleveland, Ohio, USA.|Department of Medicine, University Hospitals Case Medical Center and Center for AIDS Research (CFAR), Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Chelsey J
authors.initials: CJ
authors.lastname: Judge
authors.affiliation: Department of Medicine, University Hospitals Case Medical Center and Center for AIDS Research (CFAR), Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Lenche
authors.initials: L
authors.lastname: Kostadinova
authors.affiliation: Department of Medicine, University of Cincinnati Medical Center, Cincinnati, Ohio, USA.
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Sherman
authors.affiliation: Weill Cornell Medical College, New York, New York, USA.|Hamad Healthcare Quality Institute and Hamad Medical Corporation, Doha, Qatar.
authors.forename: Adeel A
authors.initials: AA
authors.lastname: Butt
authors.affiliation: Department of Pathology, Cleveland VA Medical Center, Case Western Reserve University, Cleveland, Ohio, USA.|Department of Medicine, University Hospitals Case Medical Center and Center for AIDS Research (CFAR), Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Yngve
authors.initials: Y
authors.lastname: Falck-Ytter
authors.affiliation: School of Health and Rehabilitation, Division of Medical Laboratory Science, The Ohio State University, Columbus, Ohio, USA.
authors.forename: Nicholas T
authors.initials: NT
authors.lastname: Funderburg
authors.affiliation: Rush University Medical Center, Chicago, Illinois, USA: and.
authors.forename: Alan L
authors.initials: AL
authors.lastname: Landay
authors.affiliation: Department of Medicine, University Hospitals Case Medical Center and Center for AIDS Research (CFAR), Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Lederman
authors.affiliation: Department of Medicine, University Hospitals Case Medical Center and Center for AIDS Research (CFAR), Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Scott F
authors.initials: SF
authors.lastname: Sieg
authors.affiliation: Center for Infection Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Johan K
authors.initials: JK
authors.lastname: Sandberg
authors.affiliation: Department of Pathology, Cleveland VA Medical Center, Case Western Reserve University, Cleveland, Ohio, USA; dda3@case.edu.|Department of Medicine, University Hospitals Case Medical Center and Center for AIDS Research (CFAR), Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Donald D
authors.initials: DD
authors.lastname: Anthony
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000276:immunology; D019002:CD56 Antigen / Q000276:immunology*; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D015497:HIV-1 / Q000276:immunology; D019698:Hepatitis C, Chronic / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D006801:Humans; D015851:Interleukin-7 / Q000276:immunology*; D053699:Interleukin-7 Receptor alpha Subunit / Q000276:immunology*; D007694:Killer Cells, Natural; D008297:Male; D008875:Middle Aged; D050799:STAT5 Transcription Factor / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D019002:CD56 Antigen; C508605:IL7 protein, human; C000620371:IL7R protein, human; D015851:Interleukin-7; D053699:Interleukin-7 Receptor alpha Subunit; C522918:NCAM1 protein, human; D050799:STAT5 Transcription Factor
keywords: IFN-γ; cellular immunity; host defense; innate immunity; viral immunity