Renner 2015 Eur J Immunol
|Renner K, Geiselhöringer AL, Fante M, Bruss C, Färber S, Schönhammer G, Peter K, Singer K, Andreesen R, Hoffmann P, Oefner P, Herr W, Kreutz M (2015) Metabolic plasticity of human T cells: Preserved cytokine production under glucose deprivation or mitochondrial restriction, but 2-deoxy-glucose affects effector functions. Eur J Immunol 45:2504-16.|
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.
• Keywords: 2-deoxy-glucose, ATP, Cytokines, Glucose deprivation, Human CD4 T cells, Human CD8 T cells, Metabolism, Mitochondrial inhibition
Labels: MiParea: Respiration
Organism: Human Tissue;cell: Blood cells, Lymphocyte Preparation: Intact cells
Coupling state: LEAK, ROUTINE, ET