NK cells acquire CCR5 and CXCR4 by trogocytosis in people living with HIV-1

NK cells play a major role in the antiviral immune response, including against HIV-1. HIV patients have impaired NK cell activity with decrease in CD56dim NK cells and increase in CD56-CD16+ subset and recently it has been proposed that a population of CD56+NKG2C+KIR+CD57+ cells represents antiviral...

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Bibliographic Details
Published inbioRxiv
Main Authors Villalba, Martin, Dang-Nghiem Vo, Leventoux, Nicolas, Campos-Mora, Mauricio, Gimenez, Sandrine, Corbeau, Pierre
Format Paper
LanguageEnglish
Published Cold Spring Harbor Cold Spring Harbor Laboratory Press 23.12.2021
Subjects
Antigens
Antiretroviral therapy
CCR5 protein
CD16 antigen
CD4 antigen
CD56 antigen
CD57 antigen
Cell lines
CXCR4 protein
Degranulation
HIV
Human immunodeficiency virus
Killer cell immunoglobulin-like receptors
Lymphocytes T
Natural killer cells
NKG2 antigen
Plasma membranes
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Summary:NK cells play a major role in the antiviral immune response, including against HIV-1. HIV patients have impaired NK cell activity with decrease in CD56dim NK cells and increase in CD56-CD16+ subset and recently it has been proposed that a population of CD56+NKG2C+KIR+CD57+ cells represents antiviral memory NK cells. Antiretroviral therapy (ART) partly restores the functional activity of this lymphocyte lineage. NK cells when interacting with their targets can gain antigens from them by the process of trogocytosis. Here we show that NK cells can obtain CCR5 and CXCR4, but barely CD4, from T cell lines by trogocytosis in vitro. By UMAP (Uniform Manifold Approximation and Projection), we show that aviremic HIV patients have unique NK cell clusters that encompass for cells expressing CCR5, NKG2C and KIRs, but lack CD57 expression. Viremic patients have a larger proportion of CXCR4+ and CCR5+ NK cells than healthy donors (HD) and this is largely increased in CD107+ cells, suggesting a link between degranulation and trogocytosis. In agreement, UMAP identified a specific NK cell cluster in viremic HIV patients, which contains most of the CD107a+, CCR5+ and CXCR4+ cells. However, this cluster lacks NKG2C expression. Therefore, NK cells can gain CCR5 and CXCR4 by trogocytosis, which depends on degranulation. Competing Interest Statement The authors have declared no competing interest.
DOI:10.1101/2021.12.21.473773