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 2014 Wolters Kluwer Health, Lippincott Williams Wilkins
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 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 Group:||Clinical health|
|Objective Field:||Clinical health not elsewhere classified|
|UTAS Author:||Henstridge, DC (Mr Darren Henstridge)|
|Web of Science® Times Cited:||84|
|Deposited By:||Health Sciences|
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