CD56NK IL-7Rα expression negatively associates with HCV level, and IL-7-induced NK function is impaired during HCV and HIV infections.

TitleCD56NK IL-7Rα expression negatively associates with HCV level, and IL-7-induced NK function is impaired during HCV and HIV infections.
Publication TypeJournal Article
Year of Publication2017
AuthorsJudge CJ, Kostadinova L, Sherman KE, Butt AA, Falck-Ytter Y, Funderburg NT, Landay AL, Lederman MM, Sieg SF, Sandberg JK, Anthony DD
JournalJ Leukoc Biol
Volume102
Issue1
Pagination171-184
Date Published2017 Jul
ISSN1938-3673
KeywordsAdult, Aged, Aged, 80 and over, Antigens, CD, CD56 Antigen, Female, Gene Expression Regulation, Hepatitis C, Chronic, HIV Infections, HIV-1, Humans, Interleukin-7, Interleukin-7 Receptor alpha Subunit, Killer Cells, Natural, Male, Middle Aged, Signal Transduction, STAT5 Transcription Factor
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 CD56CD16(CD56) subset. Here, we measured CD127 expression on CD56, CD56CD16(CD56), or CD56CD16(CD56) 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 CD56NK 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 CD56NK 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 CD56NK cells, and this effect was impaired in HCV- and HIV-infected subjects. Whereas IL-7-stimulated CD56NK 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.

DOI10.1189/jlb.5A1116-456R
Alternate JournalJ. Leukoc. Biol.
PubMed ID28400540
PubMed Central IDPMC5470838
Grant ListI01 BX001894 / BX / BLRD VA / United States
UM1 AI069501 / AI / NIAID NIH HHS / United States
R21 AI100809 / AI / NIAID NIH HHS / United States
U01 AI068636 / AI / NIAID NIH HHS / United States
UM1 AI106701 / AI / NIAID NIH HHS / United States