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

journal contribution
posted on 2023-05-20, 04:44 authored by Palmer, CS, Ostrowski, M, Gouillou, M, Tsai, L, Yu, D, Zhou, J, Darren HenstridgeDarren Henstridge, Maisa, A, Hearps, AC, Lewin, SR, Landay, A, Jaworowski, A, McCune, JM, Crowe, SM

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.

History

Publication title

AIDS

Volume

28

Pagination

297-309

ISSN

0269-9370

Department/School

School of Health Sciences

Publisher

Lippincott Williams & Wilkins

Place of publication

530 Walnut St, Philadelphia, USA, Pa, 19106-3621

Rights statement

Copyright 2014 Wolters Kluwer Health, Lippincott Williams Wilkins

Repository Status

  • Restricted

Socio-economic Objectives

Clinical health not elsewhere classified