Elevated CD4+ T-cell glucose metabolism in HIV+ women with diabetes mellitus. (1st August 2022)

• Record Type: Journal Article
• Authors: Butterfield, Tiffany R.; Hanna, David B.; Kaplan, Robert C.; Xue, Xiaonan; Kizer, Jorge R.; Durkin, Helen G.; Kassaye, Seble G.; Nowicki, Marek; Tien, Phyllis C.; Topper, Elizabeth T.; Floris-Moore, Michelle A.; Titanji, Kehmia; Fischl, Margaret A.; Heath, Sonya; Palmer, Clovis S.; Landay, Alan L.; Anzinger, Joshua J.
• Is Part Of: AIDS. Volume 36:Number 10(2022)
• Page Start: 1327
• Page End: 1336
• Publication Date: 2022-08-01
• Subjects: CD4+ T cells -- diabetes mellitus -- HIV -- immunometabolism; AIDS (Disease) -- Periodicals; Acquired Immunodeficiency Syndrome; AIDS (Disease); Periodicals; Periodicals; 616.9792005
• DOI: 10.1097/QAD.0000000000003272
• Languages: English
• ISSNs: 0269-9370

Abstract

Abstract : 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.