title: Metabolic plasticity of human T cells: Preserved cytokine production under glucose deprivation or mitochondrial restriction, but 2-deoxy-glucose affects effector functions.
abstract: The strong link between T-cell metabolism and effector functions is well characterized in the murine system but hardly investigated in human T cells. Therefore, we analyzed glycolytic and mitochondrial activity in correlation to function in activated human CD4 and CD8 T cells. Glycolysis was barely detectable upon stimulation but accelerated beyond 24 h, whereas mitochondrial activity was elevated immediately in both T-cell populations. Glucose deprivation or mitochondrial restriction reduced proliferation, had only a transient impact on "on-blast formation" and no impact on viability, IFN-γ, IL-2, IL-4, and IL-10 production, whereas TNF was reduced. Similar results were obtained in bulk T cells and T-cell subsets. Elevated respiration under glucose restriction demonstrated metabolic flexibility. Administration of the glycolytic inhibitor 2-deoxy-glucose suppressed both glycolysis and respiration and exerted a strong impact on cytokine production that persisted for IFN-γ after removal of 2-deoxy-glucose. Taken together, glycolytic or mitochondrial restriction alone compromised proliferation of human T cells, but barely affected their effector functions. In contrast, effector functions were severely affected by 2-deoxy-glucose treatment.
authors.affiliation: Department of Internal Medicine III, University Hospital Regensburg, Regensburg, Germany.|Regensburg Center for Interventional Immunology (RCI), Regensburg, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Renner
authors.affiliation: Department of Internal Medicine III, University Hospital Regensburg, Regensburg, Germany.|Regensburg Center for Interventional Immunology (RCI), Regensburg, Germany.
authors.forename: Anna-Lena
authors.initials: AL
authors.lastname: Geiselhöringer
authors.affiliation: Department of Internal Medicine III, University Hospital Regensburg, Regensburg, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Fante
authors.affiliation: Department of Internal Medicine III, University Hospital Regensburg, Regensburg, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Bruss
authors.affiliation: Department of Internal Medicine III, University Hospital Regensburg, Regensburg, Germany.|Regensburg Center for Interventional Immunology (RCI), Regensburg, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Färber
authors.affiliation: Department of Internal Medicine III, University Hospital Regensburg, Regensburg, Germany.|Regensburg Center for Interventional Immunology (RCI), Regensburg, Germany.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Schönhammer
authors.affiliation: Department of Internal Medicine III, University Hospital Regensburg, Regensburg, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Peter
authors.affiliation: Department of Internal Medicine III, University Hospital Regensburg, Regensburg, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Singer
authors.affiliation: Department of Internal Medicine III, University Hospital Regensburg, Regensburg, Germany.|Regensburg Center for Interventional Immunology (RCI), Regensburg, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Andreesen
authors.affiliation: Department of Internal Medicine III, University Hospital Regensburg, Regensburg, Germany.|Regensburg Center for Interventional Immunology (RCI), Regensburg, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Hoffmann
authors.affiliation: Institute of Functional Genomics, University Hospital of Regensburg, Regensburg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Oefner
authors.affiliation: Department of Internal Medicine III, University Hospital Regensburg, Regensburg, Germany.|Regensburg Center for Interventional Immunology (RCI), Regensburg, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Herr
authors.affiliation: Department of Internal Medicine III, University Hospital Regensburg, Regensburg, Germany.|Regensburg Center for Interventional Immunology (RCI), Regensburg, Germany.
authors.forename: Marina
authors.initials: M
authors.lastname: Kreutz
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D003847:Deoxyglucose / Q000494:pharmacology*; D005947:Glucose / Q000172:deficiency*; D006019:Glycolysis / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology; D007376:Interleukin-2 / Q000096:biosynthesis / Q000276:immunology; D015847:Interleukin-4 / Q000096:biosynthesis / Q000276:immunology; D008928:Mitochondria / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D010085:Oxidative Phosphorylation / Q000187:drug effects; D061251:Primary Cell Culture; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology
chemical_list: C508598:IL4 protein, human; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma; D003847:Deoxyglucose; D005947:Glucose
keywords: 2-deoxy-glucose; ATP; Cytokines; Glucose deprivation; Human CD4 T cells; Human CD8 T cells; Metabolism; Mitochondrial inhibition