AIDS

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AIDS:
doi: 10.1097/QAD.0000000000000128
Basic Science

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

Palmer, Clovis S.a; Ostrowski, Matiasb; Gouillou, Maelennc; Tsai, Louisd; Yu, Did; Zhou, Jinglinga; Henstridge, Darren C.e; Maisa, Annaa; Hearps, Anna C.a,f; Lewin, Sharon R.a,f,g; Landay, Alanh; Jaworowski, Anthonya,f; McCune, Joseph M.i; Crowe, Suzanne M.a,f,g

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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 HLA-DR, were measured by flow cytometry.

Results: The surface expression of the Glut1 is up-regulated in CD4+ T cells in HIV-infected 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 Lippincott Williams & Wilkins, Inc.

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