1. CD4+ T cells expressing CX3CR1, GPR56, with variable CD57 are associated with cardiometabolic diseases in persons with HIV
- Author
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Wanjalla, Celestine N, Gabriel, Curtis L, Fuseini, Hubaida, Bailin, Samuel S, Mashayekhi, Mona, Simmons, Joshua, Warren, Christopher M, Glass, David R, Oakes, Jared, Gangula, Rama, Wilfong, Erin, Priest, Stephen, Temu, Tecla, Newell, Evan W, Pakala, Suman, Kalams, Spyros A, Gianella, Sara, Smith, David, Harrison, David G, Mallal, Simon A, and Koethe, John R
- Subjects
Medical Microbiology ,Biomedical and Clinical Sciences ,Immunology ,Prevention ,Infectious Diseases ,Diabetes ,Digestive Diseases ,Liver Disease ,HIV/AIDS ,Sexually Transmitted Infections ,Aetiology ,2.1 Biological and endogenous factors ,Infection ,Good Health and Well Being ,Humans ,Calcium ,Cardiovascular Diseases ,CD4-Positive T-Lymphocytes ,CX3C Chemokine Receptor 1 ,Cytomegalovirus ,Risk Factors ,HIV Infections ,T-Lymphocyte Subsets ,CD4 T cells ,CGC ,HIV ,cardiometabolic disease ,cytomegalovirus ,Biochemistry and cell biology ,Genetics - Abstract
Persons with HIV (PWH) on long-term antiretroviral therapy (ART) have a higher incidence and prevalence of cardiometabolic diseases attributed, in part, to persistent inflammation despite viral suppression. In addition to traditional risk factors, immune responses to co-infections such as cytomegalovirus (CMV) may play an unappreciated role in cardiometabolic comorbidities and offer new potential therapeutic targets in a subgroup of individuals. We assessed the relationship of CX3CR1+, GPR56+, and CD57+/- T cells (termed CGC+) with comorbid conditions in a cohort of 134 PWH co-infected with CMV on long-term ART. We found that PWH with cardiometabolic diseases (non-alcoholic fatty liver disease, calcified coronary arteries, or diabetes) had higher circulating CGC+CD4+ T cells compared to metabolically healthy PWH. The traditional risk factor most correlated with CGC+CD4+ T cell frequency was fasting blood glucose, as well as starch/sucrose metabolites. While unstimulated CGC+CD4+ T cells, like other memory T cells, depend on oxidative phosphorylation for energy, they exhibited higher expression of carnitine palmitoyl transferase 1A compared to other CD4+ T cell subsets, suggesting a potentially greater capacity for fatty acid β-oxidation. Lastly, we show that CMV-specific T cells against multiple viral epitopes are predominantly CGC+. Together, this study suggests that among PWH, CGC+ CD4+ T cells are frequently CMV-specific and are associated with diabetes, coronary arterial calcium, and non-alcoholic fatty liver disease. Future studies should assess whether anti-CMV therapies could reduce cardiometabolic disease risk in some individuals.
- Published
- 2023