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

Palmer, C, Ostrowski, M, Gouillou, M, et al, and , 2014, 'Increased glucose metabolic activity is associated with CD4+ T-cell activation and depletion during chronic HIV infection', AIDS, vol. 28, no. 3, pp. 297-309.


Document type: Journal Article
Collection: Journal Articles

Title Increased glucose metabolic activity is associated with CD4+ T-cell activation and depletion during chronic HIV infection
Author(s) Palmer, C
Ostrowski, M
Gouillou, M
et al,
,
Year 2014
Journal name AIDS
Volume number 28
Issue number 3
Start page 297
End page 309
Total pages 13
Publisher Lippincott Williams and Wilkins
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, intrac ellular 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. © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins.
Subject Infectious Diseases
Cellular Immunology
Keyword(s) CD4 cells +
Combination antiretroviral therapy
Glucose
Glucose transporter-1
HIV
Immune activation
Inflammation
Lymphocytes
Metabolism
DOI - identifier 10.1097/QAD.0000000000000128
ISSN 0269-9370
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