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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.<\/jats:p>","DOI":"10.1093\/jimmun\/vkae054","type":"journal-article","created":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T17:23:19Z","timestamp":1741108999000},"page":"516-531","source":"Crossref","is-referenced-by-count":6,"title":["CD3+ T-cell: CD14+ monocyte complexes are dynamic and increased with HIV and glucose intolerance"],"prefix":"10.1093","volume":"214","author":[{"given":"Laventa M","family":"Obare","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, Vanderbilt University Medical Center , Nashville, TN,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua","family":"Simmons","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Vanderbilt University Medical Center , Nashville, 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