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BACKGROUND: Natural killer (NK) cells are an important type of effector cell in the innate immune response, and also have a role in regulation of the adaptive immune response. Several studies have indicated that NK cells may influence CD4+ T cells during HIV infection. METHODS: In total, 51 HIV-infected individuals and 15 healthy controls participated in this study. We performed the flow cytometry assays and real-time PCR for the phenotypic analysis and the functional assays of NK cell-mediated deletion of CD4+ T cells, phosphorylation of nuclear factor-κB (NF-κB/p65) and the intervention of metformin. RESULTS: Here we detected high CD54 expression on CD4+ T cells in HIV-infected individuals, and demonstrate that upregulated CD54 is associated with disease progression in individuals infected with HIV. We also show that CD54 expression leads to the deletion of CD4+ T cells by NK cells in vitro, and that this is modulated by NF-κB/p65 signaling. Further, we demonstrate that metformin can suppress CD54 expression on CD4+ T cells by inhibiting NF-κB/p65 phosphorylation. CONCLUSIONS: Our data suggest that further studies to evaluate the potential role of metformin as adjunctive therapy to reconstitute immune function in HIV-infected individuals are warranted.

Original publication

DOI

10.1093/infdis/jiz413

Type

Journal article

Journal

J Infect Dis

Publication Date

06/11/2019

Volume

220

Pages

1892 - 1903

Keywords

CD4+ T cells, CD54, HIV, NK cell-mediated killing, Adult, CD4 Lymphocyte Count, CD4-Positive T-Lymphocytes, Cell Communication, Cytotoxicity, Immunologic, Disease Progression, Female, Gene Expression, HIV Infections, HIV-1, Host-Pathogen Interactions, Humans, Immunophenotyping, Intercellular Adhesion Molecule-1, Killer Cells, Natural, Lymphocyte Activation, Male, Metformin, NF-kappa B, Phosphorylation, Viral Load, Young Adult