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

Area of Science:

• Immunology
• Cellular Biology
• Metabolic Disease Research

Background:

• Persistent systemic inflammation is a known risk factor for cardiometabolic diseases.
• The role of specific immune cell interactions, like cell-cell complexes, in these conditions is not well understood.
• Exclusion of cell doublets in analyses limits insight into disease-associated immune phenotypes.

Purpose of the Study:

• To investigate the characteristics and relevance of circulating CD3+ T cell: CD14+ monocyte complexes in disease states.
• To utilize controlled human immunodeficiency virus (HIV) cohorts as a model for chronic inflammation and immune cell interactions.
• To explore the association of these complexes with diabetes and inflammation.

Main Methods:

• Analysis of well-characterized clinical cohorts, including individuals with controlled HIV.
• Flow cytometry and immune phenotyping to identify and quantify CD3+ T cell: CD14+ monocyte complexes.
• Assessment of cytokine expression, glucose utilization, and viral load within these complexes.

Main Results:

• Circulating CD3+ T cell: CD14+ monocyte complexes are dynamic, biologically relevant, and increased in individuals with diabetes.
• These complexes form functional immune synapses with elevated proinflammatory cytokine expression and enhanced glucose utilization.
• In persons with HIV, these complexes harbor more HIV copies than individual cells, suggesting a role in viral persistence.

Conclusions:

• Circulating CD3+ T cell: CD14+ monocyte pairs represent significant cellular interactions contributing to inflammation and cardiometabolic disease pathogenesis.
• Chronic viral infections, such as HIV, may contribute to the formation or maintenance of these complexes.
• These findings open avenues for investigating the role of T cell-monocyte complexes in immune-mediated diseases like HIV and diabetes.