title: Cell surface Glut1 levels distinguish human CD4 and CD8 T lymphocyte subsets with distinct effector functions.
abstract: CD4 and CD8 T lymphocyte activation requires the generation of sufficient energy to support new biosynthetic demands. Following T cell receptor (TCR) engagement, these requirements are met by an increased glycolysis, due, at least in part, to induction of the Glut1 glucose transporter. As Glut1 is upregulated on tumor cells in response to hypoxia, we assessed whether surface Glut1 levels regulate the antigen responsiveness of human T lymphocytes in both hypoxic and atmospheric oxygen conditions. Notably, Glut1 upregulation in response to TCR stimulation was significantly higher in T lymphocytes activated under hypoxic as compared to atmospheric oxygen conditions. Furthermore, TCR-stimulated human T lymphocytes sorted on the basis of Glut1-Lo and Glut1-Hi profiles maintained distinct characteristics, irrespective of the oxygen tension. While T cells activated in hypoxia divided less than those activated in atmospheric oxygen, Glut1-Hi lymphocytes exhibited increased effector phenotype acquisition, augmented proliferation, and an inverted CD4/CD8 ratio in both oxygen conditions. Moreover, Glut1-Hi T lymphocytes exhibited a significantly enhanced ability to produce IFN-γ and this secretion potential was completely dependent on continued glycolysis. Thus, Glut1 surface levels identify human T lymphocytes with distinct effector functions in both hypoxic and atmospheric oxygen tensions.
authors.affiliation: Institut de Génétique Moléculaire de Montpellier, Centre National de la Recherche Scientifique UMR5535, Université de Montpellier, F-34293 Montpellier, France.
authors.forename: Gaspard
authors.initials: G
authors.lastname: Cretenet
authors.affiliation: Institut de Génétique Moléculaire de Montpellier, Centre National de la Recherche Scientifique UMR5535, Université de Montpellier, F-34293 Montpellier, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Clerc
authors.affiliation: Institut de Génétique Moléculaire de Montpellier, Centre National de la Recherche Scientifique UMR5535, Université de Montpellier, F-34293 Montpellier, France.
authors.forename: Maria
authors.initials: M
authors.lastname: Matias
authors.affiliation: Institut de Génétique Moléculaire de Montpellier, Centre National de la Recherche Scientifique UMR5535, Université de Montpellier, F-34293 Montpellier, France.
authors.forename: Severine
authors.initials: S
authors.lastname: Loisel
authors.affiliation: Institut de Génétique Moléculaire de Montpellier, Centre National de la Recherche Scientifique UMR5535, Université de Montpellier, F-34293 Montpellier, France.
authors.forename: Marco
authors.initials: M
authors.lastname: Craveiro
authors.affiliation: Institut de Génétique Moléculaire de Montpellier, Centre National de la Recherche Scientifique UMR5535, Université de Montpellier, F-34293 Montpellier, France.
authors.forename: Leal
authors.initials: L
authors.lastname: Oburoglu
authors.affiliation: Institut de Génétique Moléculaire de Montpellier, Centre National de la Recherche Scientifique UMR5535, Université de Montpellier, F-34293 Montpellier, France.
authors.forename: Sandrina
authors.initials: S
authors.lastname: Kinet
authors.affiliation: Institut de Génétique Moléculaire de Montpellier, Centre National de la Recherche Scientifique UMR5535, Université de Montpellier, F-34293 Montpellier, France.
authors.forename: Cédric
authors.initials: C
authors.lastname: Mongellaz
authors.affiliation: Institut de Génétique Moléculaire de Montpellier, Centre National de la Recherche Scientifique UMR5535, Université de Montpellier, F-34293 Montpellier, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Dardalhon
authors.affiliation: Institut de Génétique Moléculaire de Montpellier, Centre National de la Recherche Scientifique UMR5535, Université de Montpellier, F-34293 Montpellier, France.
authors.forename: Naomi
authors.initials: N
authors.lastname: Taylor
mesh_terms: D000332:Aerobiosis; D000693:Anaerobiosis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D051272:Glucose Transporter Type 1 / Q000032:analysis*; D006019:Glycolysis; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008213:Lymphocyte Activation; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology*
chemical_list: D051272:Glucose Transporter Type 1; D011948:Receptors, Antigen, T-Cell; C495677:SLC2A1 protein, human; D007371:Interferon-gamma