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CD56 bright NK IL-7Rα expression negatively associates with HCV level, and IL-7-induced NK function is impaired during HCV and HIV infections.
- Source :
-
Journal of leukocyte biology [J Leukoc Biol] 2017 Jul; Vol. 102 (1), pp. 171-184. Date of Electronic Publication: 2017 Apr 11. - Publication Year :
- 2017
-
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 CD56 <superscript>bright</superscript> CD16 <superscript>dim/-</superscript> (CD56 <superscript>bright</superscript> ) subset. Here, we measured CD127 expression on CD56 <superscript>bright</superscript> , CD56 <superscript>dim</superscript> CD16 <superscript>+</superscript> (CD56 <superscript>dim</superscript> ), or CD56 <superscript>neg</superscript> CD16 <superscript>+</superscript> (CD56 <superscript>neg</superscript> ) 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 CD56 <superscript>bright</superscript> 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 <superscript>bright</superscript> 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 <superscript>bright</superscript> NK cells, and this effect was impaired in HCV- and HIV-infected subjects. Whereas IL-7-stimulated CD56 <superscript>bright</superscript> 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.<br /> (© Society for Leukocyte Biology.)
- Subjects :
- Adult
Aged
Aged, 80 and over
Antigens, CD immunology
Female
HIV Infections pathology
HIV Infections therapy
HIV-1 immunology
Hepatitis C, Chronic pathology
Hepatitis C, Chronic therapy
Humans
Killer Cells, Natural
Male
Middle Aged
STAT5 Transcription Factor immunology
CD56 Antigen immunology
Gene Expression Regulation immunology
HIV Infections immunology
Hepatitis C, Chronic immunology
Interleukin-7 immunology
Interleukin-7 Receptor alpha Subunit immunology
Signal Transduction immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1938-3673
- Volume :
- 102
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of leukocyte biology
- Publication Type :
- Academic Journal
- Accession number :
- 28400540
- Full Text :
- https://doi.org/10.1189/jlb.5A1116-456R