title: Early changes in the metabolic profile of activated CD8(+) T cells.
abstract: Antigenic stimulation of the T cell receptor (TCR) initiates a change from a resting state into an activated one, which ultimately results in proliferation and the acquisition of effector functions. To accomplish this task, T cells require dramatic changes in metabolism. Therefore, we investigated changes of metabolic intermediates indicating for crucial metabolic pathways reflecting the status of T cells. Moreover we analyzed possible regulatory molecules required for the initiation of the metabolic changes.
  
  
  
  We found that proliferation inducing conditions result in an increase in key glycolytic metabolites, whereas the citric acid cycle remains unaffected. The upregulation of glycolysis led to a strong lactate production, which depends upon AKT/PKB, but not mTOR. The observed upregulation of lactate dehydrogenase results in increased lactate production, which we found to be dependent on IL-2 and to be required for proliferation. Additionally we observed upregulation of Glucose-transporter 1 (GLUT1) and glucose uptake upon stimulation, which were surprisingly not influenced by AKT inhibition.
  
  
  
  Our findings suggest that AKT plays a central role in upregulating glycolysis via induction of lactate dehydrogenase expression, but has no impact on glucose uptake of T cells. Furthermore, under apoptosis inducing conditions, T cells are not able to upregulate glycolysis and induce lactate production. In addition maintaining high glycolytic rates strongly depends on IL-2 production.
authors.affiliation: Institute of Molecular and Clinical Immunology, Otto-von-Guericke-University, Magdeburg, Germany. clemens.cammann@med.ovgu.de.
authors.forename: Clemens
authors.initials: C
authors.lastname: Cammann
authors.affiliation: Max-Planck-Institute for Dynamics of Complex Technical Systems, Magdeburg, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Rath
authors.affiliation: Max-Planck-Institute for Dynamics of Complex Technical Systems, Magdeburg, Germany.
authors.forename: Udo
authors.initials: U
authors.lastname: Reichl
authors.affiliation: Department of Experimental Pediatrics, Otto-von-Guericke-University, Magdeburg, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Lingel
authors.affiliation: Department of Experimental Pediatrics, Otto-von-Guericke-University, Magdeburg, Germany.
authors.forename: Monika
authors.initials: M
authors.lastname: Brunner-Weinzierl
authors.affiliation: Institute of Molecular and Clinical Immunology, Otto-von-Guericke-University, Magdeburg, Germany.
authors.forename: Luca
authors.initials: L
authors.lastname: Simeoni
authors.affiliation: Institute of Molecular and Clinical Immunology, Otto-von-Guericke-University, Magdeburg, Germany.|Department of Immune Control, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Burkhart
authors.initials: B
authors.lastname: Schraven
authors.affiliation: Institute of Molecular and Clinical Immunology, Otto-von-Guericke-University, Magdeburg, Germany.|Department of Nephrology and Hypertension, Diabetes and Endocrinology, Otto-von-Guericke University, Magdeburg, Germany.
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Lindquist
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D060908:CTLA-4 Antigen / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D004579:Electron Transport / Q000187:drug effects; D006019:Glycolysis / Q000187:drug effects; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D007773:Lactates / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D055432:Metabolomics; D008822:Mice, Transgenic; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000906:Antibodies; D060908:CTLA-4 Antigen; D007376:Interleukin-2; D007773:Lactates; D000255:Adenosine Triphosphate; D007770:L-Lactate Dehydrogenase; D051057:Proto-Oncogene Proteins c-akt
keywords: AKT/PKB; Aerobic glycolysis; Lactate; T-cell activation