Renner, Kathrin and Geiselhoeringer, Anna-Lena and Fante, Matthias and Bruss, Christina and Faerber, Stephanie and Schoenhammer, Gabriele and Peter, Katrin and Singer, Katrin and Andreesen, Reinhard and Hoffmann, Petra and Oefner, Peter and Herr, Wolfgang and Kreutz, Marina (2015) Metabolic plasticity of human T cells: Preserved cytokine production under glucose deprivation or mitochondrial restriction, but 2-deoxy-glucose affects effector functions. EUROPEAN JOURNAL OF IMMUNOLOGY, 45 (9). pp. 2504-2516. ISSN 0014-2980, 1521-4141
Full text not available from this repository. (Request a copy)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-gamma, 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-gamma 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | LYMPHOCYTE ACTIVATION; IMMUNE CELLS; MEMORY; GLYCOLYSIS; GLUTAMINE; 2-DEOXY-D-GLUCOSE; INHIBITION; MIGRATION; REQUIRES; TARGET; 2-deoxy-glucose; ATP; Cytokines; Glucose deprivation; Human CD4 T cells; Human CD8 T cells; Metabolism; Mitochondrial inhibition |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Institut für Funktionelle Genomik > Lehrstuhl für Funktionelle Genomik (Prof. Oefner) Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 12 Jun 2019 13:10 |
| Last Modified: | 12 Jun 2019 13:10 |
| URI: | https://pred.uni-regensburg.de/id/eprint/4912 |
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