Persistence of a Skewed Repertoire of NK Cells in People with HIV-1 on Long-Term Antiretroviral Therapy
Year: 2024
Type: article
Study design: Observational Study
Abstract: HIV-1 infection greatly alters the NK cell phenotypic and functional repertoire. This is highlighted by the expansion of a rare population of FcRγ- NK cells exhibiting characteristics of traditional immunologic memory in people with HIV (PWH). Although current antiretroviral therapy (ART) effectively controls HIV-1 viremia and disease progression, its impact on HIV-1-associated NK cell abnormalities remains unclear. To address this, we performed a longitudinal analysis detailing conventional and memory-like NK cell characteristics in n = 60 PWH during the first 4 y of ART. Throughout this regimen, a skewed repertoire of cytokine unresponsive FcRγ- memory-like NK cells persisted and accompanied an overall increase in NK surface expression of CD57 and KLRG1, suggestive of progression toward immune senescence. These traits were linked to elevated serum inflammatory biomarkers and increasing Ab titers to human CMV, with human CMV viremia detected in approximately one-third of PWH at years 1-4 of ART. Interestingly, 40% of PWH displayed atypical NK cell subsets, representing intermediate stages of NK-poiesis based on single-cell multiomic trajectory analysis. Our findings indicate that NK cell irregularities persist in PWH despite long-term ART, underscoring the need to better understand the causative mechanisms that prevent full restoration of immune health in PWH.
Source: The Journal of Immunology
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Funders: American Association of Immunologists, Emory University, Harvard University, Harvard University Center for AIDS Research, University of Pittsburgh, ACT Government, National Institutes of Health, Center for AIDS Research, University of Washington, National Heart, Lung, and Blood Institute, National Institute of Allergy and Infectious Diseases
Awards: G1575283533, G1819583291, G2127051194, G285461174, G2898952431, G3810609436, G3922356, G4166928756, G4553935269, G4885028645, G5747858550, G5863844756, G6186512954, G679335189, G681742546, G693265041, G7152846654, G7785852513, G7867776981, Illumina NovaSeq 6000 High Throughput DNA Sequencer for Emory University, G857487509, G9000039438, G9000054876, G9000058579, G9000066220, G9000118633, G9000129761, G9000132212, G9000240667, G9000292181, G9000347162, Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections, Antigen-specific ‘kick and kill’ of the latent HIV reservoir using dendritic cells, Rustbelt Center for AIDS Research (Case/UHC-Pitt CFAR), AIDS Clinical Trial Group Laboratory Center, Statistical and Data Management Center (SDMC), Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections (ACTG), University of North Carolina Global HIV Prevention and Treatment Clinical Trials Unit, G90079629
OpenAlex ID: W4393317989