Cutting edge: distinct glycolytic and lipid oxidative metabolic programs are essential for effector and regulatory CD4+ T cell subsets

J Immunol. 2011 Mar 15;186(6):3299-303. doi: 10.4049/jimmunol.1003613. Epub 2011 Feb 11.

Abstract

Stimulated CD4(+) T lymphocytes can differentiate into effector T cell (Teff) or inducible regulatory T cell (Treg) subsets with specific immunological roles. We show that Teff and Treg require distinct metabolic programs to support these functions. Th1, Th2, and Th17 cells expressed high surface levels of the glucose transporter Glut1 and were highly glycolytic. Treg, in contrast, expressed low levels of Glut1 and had high lipid oxidation rates. Consistent with glycolysis and lipid oxidation promoting Teff and Treg, respectively, Teff were selectively increased in Glut1 transgenic mice and reliant on glucose metabolism, whereas Treg had activated AMP-activated protein kinase and were dependent on lipid oxidation. Importantly, AMP-activated protein kinase stimulation was sufficient to decrease Glut1 and increase Treg generation in an asthma model. These data demonstrate that CD4(+) T cell subsets require distinct metabolic programs that can be manipulated in vivo to control Treg and Teff development in inflammatory diseases.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Animals
  • Asthma / immunology
  • Asthma / metabolism
  • Asthma / pathology
  • Cell Survival / genetics
  • Cell Survival / immunology
  • Cells, Cultured
  • Disease Models, Animal
  • Glucose Transporter Type 1 / antagonists & inhibitors
  • Glucose Transporter Type 1 / genetics
  • Glucose Transporter Type 1 / metabolism
  • Glycolysis / immunology*
  • Immunophenotyping
  • Lipid Peroxidation / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism*
  • T-Lymphocytes, Helper-Inducer / cytology
  • T-Lymphocytes, Helper-Inducer / immunology*
  • T-Lymphocytes, Helper-Inducer / metabolism*
  • T-Lymphocytes, Regulatory / enzymology
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism*
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Glucose Transporter Type 1
  • Slc2a1 protein, mouse
  • mTOR protein, mouse
  • TOR Serine-Threonine Kinases
  • AMP-Activated Protein Kinases