Metabolic plasticity of human T cells: Preserved cytokine production under glucose deprivation or mitochondrial restriction, but 2‐deoxy‐glucose affects effector functions. Issue 9 (20th July 2015)

• Record Type: Journal Article
• Authors: Renner, Kathrin; Geiselhöringer, Anna‐Lena; Fante, Matthias; Bruss, Christina; Färber, Stephanie; Schönhammer, Gabriele; Peter, Katrin; Singer, Katrin; Andreesen, Reinhard; Hoffmann, Petra; Oefner, Peter; Herr, Wolfgang; Kreutz, Marina
• Is Part Of: European journal of immunology. Volume 45:Issue 9(2015:Sep.)
• Page Start: 2504
• Page End: 2516
• Publication Date: 2015-07-20
• Subjects: Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.201545473
• Languages: English
• ISSNs: 0014-2980

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>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.</p> </abstract>