期刊
AIDS
卷 36, 期 10, 页码 1327-1336出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/QAD.0000000000003272
关键词
CD4(+) T cells; diabetes mellitus; HIV; immunometabolism
资金
- University at Buffalo Clinical and Translational Science Institute award [UL1TR001412]
- Global Infectious Diseases Research Training Program [D43TW010919]
- Office of the Principal of the University of theWest Indies, Mona
- NHLBI [1R01HL148094, 1R01HL140976]
- Atlanta CRS [U01-HL146241]
- Baltimore CRS [U01HL146201]
- Bronx CRS [U01-HL146204]
- Brooklyn CRS [U01-HL146202]
- Data Analysis and Coordination Center [U01HL146193]
- Chicago-Cook County CRS [U01-HL146245]
- Chicago-Northwestern CRS [U01HL146240]
- Northern California CRS [U01-HL146242]
- Los Angeles CRS [U01-HL146333]
- Metropolitan Washington CRS [U01-HL146205]
- Miami CRS [U01-HL146203]
- Pittsburgh CRS [U01-HL146208]
- UAB-MS CRS [U01-HL146192]
- UNC CRS [U01-HL146194]
- National Heart, Lung, and Blood Institute (NHLBI)
- Eunice Kennedy Shriver National Institute Of Child Health & Human Development (NICHD)
- National Institute On Aging (NIA)
- National Institute Of Dental & Craniofacial Research (NIDCR)
- National Institute Of Allergy And Infectious Diseases (NIAID)
- National Institute Of Neurological Disorders And Stroke (NINDS)
- National Institute Of Mental Health (NIMH)
- National Institute On Drug Abuse (NIDA)
- National Institute Of Nursing Research (NINR)
- National Cancer Institute (NCI)
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)
- National Institute on Deafness and Other Communication Disorders (NIDCD)
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- National Institute on Minority Health and Health Disparities (NIMHD)
- National Institutes of Health, Office of AIDS Research (OAR)
- UCSF CTSA [UL1TR000004]
- JHU ICTR [UL1-TR003098]
- UCLA CTSI [UL1-TR001881]
- Atlanta CFAR [P30-AI050409]
- Miami CFAR [P30-AI-073961]
- UNC CFAR [P30-AI-050410]
- UAB CFAR [P30-AI027767]
- Miami CHARM [P30-MH-116867]
- [UM1 AI106701]
- [K01-HL-137557]
This study investigated the glucose metabolism of CD4(+) T cells in HIV-positive women with and without diabetes mellitus. The results showed that HIV-positive women with diabetes mellitus had elevated CD4(+) T cell glucose metabolism, and treatment of diabetes mellitus may partially correct CD4(+) T cell metabolic dysfunction.
Objective: Immune dysfunction and chronic inflammation are characteristic of HIV infection and diabetes mellitus, with CD4(+) T-cell metabolism implicated in the pathogenesis of each disease. However, there is limited information on CD4(+) T-cell metabolism in HIV+ persons with diabetes mellitus. We examined CD4(+) T-cell glucose metabolism in HIV+ women with and without diabetes mellitus. Design: A case-control study was used to compare CD4(+) T-cell glucose metabolism in women with HIV with or without diabetes mellitus. Methods: Nondiabetic (HIV+DM-, N = 20) or type 2 diabetic HIV+ women with (HIV+DM+, N = 16) or without (HIV+DMTx+, N = 18) antidiabetic treatment were identified from the WIHS and matched for age, race/ethnicity, smoking status and CD4(+) cell count. CD4(+) T-cell immunometabolism was examined by flow cytometry, microfluidic qRT-PCR of metabolic genes, and Seahorse extracellular flux analysis of stimulated CD4(+) T cells. Results: HIV+DM+ displayed a significantly elevated proportion of CD4(+) T cells expressing the immunometabolic marker GLUT1 compared with HIV+DMTx+ and HIV+DM- (P = 0.04 and P = 0.01, respectively). Relative expression of genes encoding key enzymes for glucose metabolism pathways were elevated in CD4(+) T cells of HIV+DM+ compared with HIV+DMTx+ and HIV+DM-. T-cell receptor (TCR)-activated CD4(+) T cells from HIV+DM+ showed elevated glycolysis and oxidative phosphorylation compared with HIV+DM-. Conclusion: CD4(+) T cells from HIV+DM+ have elevated glucose metabolism. Treatment of diabetes mellitus among women with HIV may partially correct CD4(+) T-cell metabolic dysfunction.
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