Metabolic plasticity of human T cells: Preserved cytokine production under glucose deprivation or mitochondrial restriction, but 2‐deoxy‐glucose affects effector functions
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Media type:
E-Article
Title:
Metabolic plasticity of human T cells: Preserved cytokine production under glucose deprivation or mitochondrial restriction, but 2‐deoxy‐glucose affects effector functions
Published in:
European Journal of Immunology, 45 (2015) 9, Seite 2504-2516
Language:
English
DOI:
10.1002/eji.201545473
ISSN:
0014-2980;
1521-4141
Origination:
Footnote:
Description:
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.