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Open Access CC BY V4.0
Journal article
CD4 T cells expressing CX3CR1, GPR56, with variable CD57 are associated with cardiometabolic diseases in persons with HIV
Frontiers in immunology, Vol.14, p.1099356
2023
PMID: 36865544
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.
Details
- Title
- CD4 T cells expressing CX3CR1, GPR56, with variable CD57 are associated with cardiometabolic diseases in persons with HIV
- Authors/Creators
- Celestine N. Wanjalla - Vanderbilt University Medical CenterCurtis L. Gabriel - Vanderbilt University Medical CenterHubaida Fuseini - Vanderbilt University Medical CenterSamuel S. Bailin - Vanderbilt University Medical CenterMona Mashayekhi - Vanderbilt University Medical CenterJoshua Simmons - Vanderbilt University Medical CenterChristopher M. Warren - Vanderbilt University Medical CenterDavid R. Glass - Fred Hutch Cancer CenterJared Oakes - Vanderbilt University Medical CenterRama Gangula - Vanderbilt University Medical CenterErin Wilfong - Vanderbilt University Medical CenterStephen Priest - Vanderbilt University Medical CenterTecla Temu - University of WashingtonEvan W. Newell - Fred Hutch Cancer CenterSuman Pakala - Vanderbilt University Medical CenterSpyros A. Kalams - Vanderbilt University Medical CenterSara Gianella - University of California San DiegoDavid Smith - University of California San DiegoDavid G. Harrison - Vanderbilt University Medical CenterSimon A. Mallal - Vanderbilt University Medical CenterJohn R. Koethe - Vanderbilt University Medical Center
- Publication Details
- Frontiers in immunology, Vol.14, p.1099356
- Grant note
- National Institute of Diabetes and Digestive and Kidney Diseases (100000062) Doris Duke Charitable Foundation (100000862) Burroughs Wellcome Fund (http://data.elsevier.com/vocabulary/SciValFunders/100000861) P30 AI110527 / NIH Tennessee Center for AIDS Research K23 HL156759; R01 DK112262; U19 AI128914; UM1 AI068618 / National Institutes of Health (http://data.elsevier.com/vocabulary/SciValFunders/100000002) Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases (100015691) National Institute of Allergy and Infectious Diseases (100000060) Cancer Research Institute (http://data.elsevier.com/vocabulary/SciValFunders/100000884) National Heart, Lung, and Blood Institute (100000050) 1021480 / Burroughs Wellcome Fund (http://data.elsevier.com/vocabulary/SciValFunders/100000861)
- Identifiers
- 991005884938107891
- Copyright
- © 2023 Wanjalla, Gabriel, Fuseini, Bailin, Mashayekhi, Simmons, Warren, Glass, Oakes, Gangula, Wilfong, Priest, Temu, Newell, Pakala, Kalams, Gianella, Smith, Harrison, Mallal and Koethe.
- Murdoch Affiliation
- Research and Innovation Office; Institute for Immunology and Infectious Diseases
- Language
- English
- Resource Type
- Journal article
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