title: Increased glucose metabolic activity is associated with CD4+ T-cell activation and depletion during chronic HIV infection.
abstract: OBJECTIVE
  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.
  
  
  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 CD4Glut1 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 CD4Glut1 T cells compared to CD4Glut1 T cells. The proportion of CD4Glut1 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.
  
  
  CONCLUSIONS
  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.
authors: aCentre for Biomedical Research, Burnet Institute, Melbourne, Australia bInstituto de Investigaciones Biomédicas en Retrovirus y SIDA. Facultad de Medicina, Buenos Aires, Argentina cCentre for Population Health, Burnet Institute, Melbourne dLaboratory of Molecular Immunomodulation, School of Biomedical Sciences, Monash University, Clayton eCellular and Molecular Metabolism Laboratory, Baker IDI Heart and Diabetes Institute fDepartment of Infectious Diseases, Monash University gInfectious Diseases Department, The Alfred hospital, Melbourne, Australia hDepartment of Immunology/Microbiology, Rush University Medical Center, Chicago, Illinois iDivision of Experimental Medicine, Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
authors: Clovis S
authors: CS
authors: Palmer
authors: Matias
authors: M
authors: Ostrowski
authors: Maelenn
authors: M
authors: Gouillou
authors: Louis
authors: L
authors: Tsai
authors: Di
authors: D
authors: Yu
authors: Jingling
authors: J
authors: Zhou
authors: Darren C
authors: DC
authors: Henstridge
authors: Anna
authors: A
authors: Maisa
authors: Anna C
authors: AC
authors: Hearps
authors: Sharon R
authors: SR
authors: Lewin
authors: Alan
authors: A
authors: Landay
authors: Anthony
authors: A
authors: Jaworowski
authors: Joseph M
authors: JM
authors: McCune
authors: Suzanne M
authors: SM
authors: Crowe
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002908:Chronic Disease; D005260:Female; D005434:Flow Cytometry; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1 / Q000032:analysis; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D055815:Young Adult
chemical_list: D015415:Biomarkers; D051272:Glucose Transporter Type 1; C495677:SLC2A1 protein, human; D005947:Glucose