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

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., and Parsons, Matthew S. (2022) Phenotypic and functional characteristics of highly differentiated CD57 +NKG2C + NK cells in HIV-1- infected individuals. Clinical and Experimental Immunology, 210 (2). pp. 163-174.

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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.

Item ID: 76299
Item Type: Article (Research - C1)
ISSN: 1365-2249
Copyright Information: © The Author(s) 2022. Published by Oxford University Press on behalf of the American Society of Animal Science. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (, which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact
Funders: National Health and Medical Research Council (NHMRC)
Projects and Grants: NHMRC Program Grant (APP1149990)
Date Deposited: 18 Oct 2022 00:51
FoR Codes: 32 BIOMEDICAL AND CLINICAL SCIENCES > 3204 Immunology > 320404 Cellular immunology @ 50%
32 BIOMEDICAL AND CLINICAL SCIENCES > 3204 Immunology > 320405 Humoural immunology and immunochemistry @ 50%
SEO Codes: 20 HEALTH > 2099 Other health > 209999 Other health not elsewhere classified @ 100%
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