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

Clovis S. Palmer, Matias Ostrowski, Maelenn Gouillou, Louis Tsai, Di Yu, Jingling Zhou, Darren C. Henstridge, Anna Maisa, Anna C. Hearps, Sharon R. Lewin, Alan Landay, Anthony Jaworowski, Joseph M. McCune, Suzanne M. Crowe

Research output: Contribution to journalArticlepeer-review

133 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)297-309
Number of pages13
JournalAIDS
Volume28
Issue number3
DOIs
StatePublished - Jan 28 2014
Externally publishedYes

Keywords

  • CD4 cells
  • Combination antiretroviral therapy
  • Glucose
  • Glucose transporter-1
  • HIV
  • Immune activation
  • Inflammation
  • Lymphocytes
  • Metabolism

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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