CD3+ T-cell: CD14+ monocyte complexes are dynamic and increased with HIV and glucose intolerance

Laventa M Obare; Joshua Simmons; Jared Oakes; Xiuqi Zhang; Cindy Nochowicz; Stephen Priest; Samuel S Bailin; Christian M Warren; Mona Mashayekhi; Heather K Beasley; Jianqiang Shao; Leslie M Meenderink; Quanhu Sheng; Joey Stolze; Rama Gangula; Tarek Absi; Yan Ru Su; Kit Neikirk; Abha Chopra; Curtis L Gabriel; Tecla Temu; Suman Pakala; Erin M Wilfong; Sara Gianella; Elizabeth J Phillips; David G Harrison; Antentor Hinton; Spyros A Kalams; Annet Kirabo; Simon A Mallal; John R Koethe; Celestine N Wanjalla

doi:10.1093/jimmun/vkae054

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CD3+ T-cell: CD14+ monocyte complexes are dynamic and increased with HIV and glucose intolerance

Journal article

Open access

Peer reviewed

CD3+ T-cell: CD14+ monocyte complexes are dynamic and increased with HIV and glucose intolerance

Laventa M Obare, Joshua Simmons, Jared Oakes, Xiuqi Zhang, Cindy Nochowicz, Stephen Priest, Samuel S Bailin, Christian M Warren, Mona Mashayekhi, Heather K Beasley, …

The Journal of immunology (1950), Vol.214(3), pp.516-531

2025

DOI: https://doi.org/10.1093/jimmun/vkae054

PMID: 40073149

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Abstract

CD3

HIV

doublets

monocyte complexes

T-cell: CD14

reservoir

diabetes

Persistent systemic inflammation is associated with an elevated risk of cardiometabolic diseases. However, the characteristics of the innate and adaptive immune systems in individuals who develop these conditions remain poorly defined. Doublets, or cell-cell complexes, are routinely eliminated from flow cytometric and other immune phenotyping analyses, which limits our understanding of their relationship to disease states. Using well-characterized clinical cohorts, including participants with controlled human immunodeficiency virus (HIV) as a model for chronic inflammation and increased immune cell interactions, we show that circulating CD14+ monocytes complexed to CD3+ T cells are dynamic, biologically relevant, and increased in individuals with diabetes after adjusting for confounding factors. The complexes form functional immune synapses with increased expression of proinflammatory cytokines and greater glucose utilization. Furthermore, in persons with HIV, the CD3+ T cell: CD14+ monocyte complexes had more HIV copies compared to matched CD14+ monocytes or CD4+ T cells alone. Our results demonstrate that circulating CD3+ T-cell: CD14+ monocyte pairs represent dynamic cellular interactions that may contribute to inflammation and cardiometabolic disease pathogenesis. CD3+ T-cell: CD14+ monocyte complexes may originate or be maintained, in part, by chronic viral infections. These findings provide a foundation for future studies investigating mechanisms linking T cell-monocyte cell-cell complexes to developing immune-mediated diseases, including HIV and diabetes.

Details

Title: CD3+ T-cell: CD14+ monocyte complexes are dynamic and increased with HIV and glucose intolerance
Authors/Creators: Laventa M Obare - Vanderbilt University Medical Center
Joshua Simmons - Vanderbilt University Medical Center
Jared Oakes - Vanderbilt University Medical Center
Xiuqi Zhang - Vanderbilt University Medical Center
Cindy Nochowicz - Vanderbilt University Medical Center
Stephen Priest - Vanderbilt University Medical Center
Samuel S Bailin - Vanderbilt University Medical Center
Christian M Warren - VA Tennessee Valley Healthcare System
Mona Mashayekhi - Vanderbilt University Medical Center
Heather K Beasley - Vanderbilt University
Jianqiang Shao - University of Iowa
Leslie M Meenderink - Vanderbilt University Medical Center
Quanhu Sheng - Vanderbilt University
Joey Stolze - Vanderbilt University
Rama Gangula - Vanderbilt University Medical Center
Tarek Absi - Vanderbilt University Medical Center
Yan Ru Su - Vanderbilt University Medical Center
Kit Neikirk - Vanderbilt University
Abha Chopra - Murdoch University
Curtis L Gabriel - Vanderbilt University Medical Center
Tecla Temu - University of Washington
Suman Pakala - Vanderbilt University Medical Center
Erin M Wilfong - Vanderbilt University Medical Center
Sara Gianella - University of California San Diego
Elizabeth J Phillips - Vanderbilt University Medical Center
David G Harrison - Vanderbilt University Medical Center
Antentor Hinton - Vanderbilt University
Spyros A Kalams - Vanderbilt University Medical Center
Annet Kirabo - Vanderbilt University
Simon A Mallal - Department of Biomedical Informatics, Vanderbilt University, Nashville, TN, United States
John R Koethe - Vanderbilt University Medical Center
Celestine N Wanjalla - Vanderbilt University Medical Center
Publication Details: The Journal of immunology (1950), Vol.214(3), pp.516-531
Publisher: Oxford University Press on behalf of The American Association of Immunologists.; OXFORD
Number of pages: 16
Grant note: 1021480 / Burroughs Wellcome
Identifiers: 991005753830507891
Murdoch Affiliation: Institute for Immunology and Infectious Diseases; Centre for Molecular Medicine and Innovative Therapeutics
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.66 HIV; 1.66.1372 HIV Comorbidities
Web Of Science research areas: Immunology
ESI research areas: Immunology