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Increased glucose metabolic activity is associated with CD4+ T-cell activation and depletion during chronic HIV infection

Citation

Palmer, CS and Ostrowski, M and Gouillou, M and Tsai, L and Yu, D and Zhou, J and Henstridge, DC and Maisa, A and Hearps, AC and Lewin, SR and Landay, A and Jaworowski, A and McCune, JM and Crowe, SM, Increased glucose metabolic activity is associated with CD4+ T-cell activation and depletion during chronic HIV infection, AIDS, 28, (3) pp. 297-309. ISSN 0269-9370 (2014) [Refereed Article]

Copyright Statement

Copyright 2014 Wolters Kluwer Health, Lippincott Williams Wilkins

DOI: doi:10.1097/QAD.0000000000000128

Abstract

Objectives: Glucose metabolism plays a fundamental role in supporting the growth, proliferation and effector functions of T cells. We investigated the impact of HIV infection on key processes that regulate glucose uptake and metabolism in primary CD4+ and CD8+ T cells.

Design and methods: Thirty-eight HIV-infected treatment-naive, 35 HIV+/ combination antiretroviral therapy, seven HIV+ long-term nonprogressors and 25 HIV control individuals were studied. Basal markers of glycolysis [e.g. glucose transporter-1 (Glut1) expression, glucose uptake, intracellular glucose-6-phosphate, and L-lactate] were measured in T cells. The cellular markers of immune activation, CD38 and HLADR, were measured by flow cytometry.

Results: The surface expression of the Glut1 is up-regulated in CD4+ T cells in HIVinfected patients compared with uninfected controls. The percentage of circulating CD4+Glut1+ T cells was significantly increased in HIV-infected patients and was not restored to normal levels following combination antiretroviral therapy. Basal markers of glycolysis were significantly higher in CD4+Glut1+ T cells compared to CD4+Glut1- T cells. The proportion of CD4+Glut1+ T cells correlated positively with the expression of the cellular activation marker, HLA-DR, on total CD4+ T cells, but inversely with the absolute CD4+ T-cell count irrespective of HIV treatment status.

Conclusion: Our data suggest that Glut1 is a potentially novel and functional marker of CD4+ T-cell activation during HIV infection. In addition, Glut1 expression on CD4+ T cells may be exploited as a prognostic marker for CD4+ T-cell loss during HIV disease progression.

Item Details

Item Type:Refereed Article
Keywords:CD4+ cells, combination antiretroviral therapy, glucose, glucose transporter-1, HIV, immune activation, inflammation, lymphocytes, metabolism, adolescent, adult, biological markers, CD4-positive T-lymphocytes, CD8-positive T-lymphocytes, female
Research Division:Biological Sciences
Research Group:Biochemistry and Cell Biology
Research Field:Cell Metabolism
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Immune System and Allergy
UTAS Author:Henstridge, DC (Mr Darren Henstridge)
ID Code:133347
Year Published:2014
Web of Science® Times Cited:54
Deposited By:Health Sciences
Deposited On:2019-06-24
Last Modified:2019-08-20
Downloads:0

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