Phenotypic and functional characteristics of highly differentiated CD57 +NKG2C + NK cells in HIV-1- infected individuals

Journal Publication ResearchOnline@JCU
Kristensen, Anne B.;Wragg, Kathleen;Vanderven, Hillary;Lee, Wen Shi;Silvers, Julie;Kent, Helen E.;Grant, Michael D.;Kelleher, Anthony D.;Juno, Jennifer A.;Kent, Stephen J.;Parsons, Matthew S.
Hillary Vanderven
Abstract

Natural killer (NK) cells are important anti-viral effector cells. The function and phenotype of the NK cells that constitute an individual’s NK cell repertoire can be influenced by ongoing and/or previous viral infections. Indeed, infection with human cytomegalovirus (HCMV) drives the expansion of a highly differentiated NK cell population characterized by expression of CD57 and the activating NKG2C receptor. This NK cell population has also been noted to occur in HIV-1-infected individuals. We evaluated the NK cells of HIV-1-infected and –uninfected individuals to determine the relative frequency of highly differentiated CD57 +NKG2C + NK cells and characterize these cells for their receptor expression and responsiveness to diverse stimuli. Highly differentiated CD57 +NKG2C + NK cells occurred at higher frequencies in HCMV-infected donors relative to HCMV-uninfected donors and were dramatically expanded in HIV-1/HCMV co-infected donors. The expanded CD57 +NKG2C + NK cell population in HIV-1-infected donors remained stable following antiretroviral therapy. CD57 +NKG2C + NK cells derived from HIV-1-infected individuals were robustly activated by antibody-dependent stimuli that contained anti-HIV-1 antibodies or therapeutic anti-CD20 antibody, and these NK cells mediated cytolysis through NKG2C. Lastly, CD57 +NKG2C + NK cells from HIV-1-infected donors were characterized by reduced expression of the inhibitory NKG2A receptor. The abundance of highly functional CD57 +NKG2C + NK cells in HIV-1-infected individuals raises the possibility that these NK cells could play a role in HIV-1 pathogenesis or serve as effector cells for therapeutic/cure strategies.

Journal

Clinical and Experimental Immunology

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Volume

210

ISBN/ISSN

1365-2249

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Issue

2

Pages Count

36

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Publisher

Blackwell Publishing

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DOI

10.1093/cei/uxac082