CD56bright NK IL-7Rα expression negatively associates with HCV level, and IL-7-induced NK function is impaired during HCV and HIV infections

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

Anthony, Donald D.¹  Lederman, Michael M.¹  Sherman, Kenneth E.¹  Falck-Ytter, Yngve¹  Sandberg, Johan K.²  Landay, Alan L.³  Kostadinova, Lenche⁵  Butt, Adeel A.⁶  Sieg, Scott F.⁷  Funderburg, Nicholas T.^1,10 

[1] ..Department of Medicine, University Hospitals Case Medical Center and Center for AIDS Research (CFAR), Case Western Reserve University, Cleveland, Ohio, USA;..Hamad Healthcare Quality Institute and Hamad Medical Corporation, Doha, Qatar;Center for Infection Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden;Department of Medicine, University Hospitals Case Medical Center and Center for AIDS Research (CFAR), Case Western Reserve University, Cleveland, Ohio, USA;Department of Medicine, University of Cincinnati Medical Center, Cincinnati, Ohio, USA;Department of Pathology, Cleveland VA Medical Center, Case Western Reserve University, Cleveland, Ohio, USA;Rush University Medical Center, Chicago, Illinois, USA: and;School of Health and Rehabilitation, Division of Medical Laboratory Science, The Ohio State University, Columbus, Ohio, USA;Weill Cornell Medical College, New York, New York, USA

关键词: cellular immunity;    innate immunity;    IFN‐;    γ    viral immunity;    host defense;   

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

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 CD56^brightCD16^dim/− (CD56^bright) subset. Here, we measured CD127 expression on CD56^bright, CD56^dimCD16⁺ (CD56^dim), or CD56^negCD16⁺ (CD56^neg) NK cell subsets of 25 uninfected donors (UD); 34 chronic HCV-infected, treatment-naiüve; 25 HIV-infected, virally suppressed on antiretroviral therapy (ART); and 42 HCV–HIV-coinfected subjects on ART. Interestingly, CD127 expression on CD56^bright NK 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 CD56^bright NK 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 CD56^bright NK cells, and this effect was impaired in HCV- and HIV-infected subjects. Whereas IL-7-stimulated CD56^bright NK 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.

【 授权许可】

CC BY