Anergic T Cells Are Metabolically Anergic
- 15 November 2009
- journal article
- Published by The American Association of Immunologists in The Journal of Immunology
- Vol. 183 (10), 6095-6101
- https://doi.org/10.4049/jimmunol.0803510
Abstract
Full T cell activation requires TCR engagement (signal 1) in the context of costimulation (signal 2). Costimulation is required for maximal expression of effector cytokines and prevention of T cell anergy. It has become increasingly clear that another major function of costimulation is to up-regulate the metabolic machinery necessary for T cell function. In this report we demonstrate that anergic T cells are metabolically anergic, in that upon full stimulation (signals 1 plus 2) they fail to up-regulate the machinery necessary to support increased metabolism. These findings suggest that one mechanism responsible for the maintenance of T cell anergy is failure to up-regulate the metabolic machinery. Furthermore, we demonstrate that by blocking leucine, glucose, and energy metabolism, T cell activation is mitigated. Additionally, inhibition of these metabolic pathways during T cell activation leads to anergy in Th1-differentiated cells. Overall, our findings extend the role of T cell metabolism in regulating T cell function.Keywords
This publication has 33 references indexed in Scilit:
- Infectious tolerance via the consumption of essential amino acids and mTOR signalingProceedings of the National Academy of Sciences of the United States of America, 2009
- Leucine stimulates protein synthesis in skeletal muscle of neonatal pigs by enhancing mTORC1 activationAmerican Journal of Physiology-Endocrinology and Metabolism, 2008
- Glucose deprivation inhibits multiple key gene expression events and effector functions in CD8+ T cellsEuropean Journal of Immunology, 2008
- Failure at the Effector Phase: Immune Barriers at the Level of the Melanoma Tumor MicroenvironmentClinical Cancer Research, 2007
- The induction and maintenance of T cell anergyClinical Immunology, 2006
- mTOR and cancer: insights into a complex relationshipNature Reviews Cancer, 2006
- Regulation of the energy sensor AMP-activated protein kinase by antigen receptor and Ca2+ in T lymphocytesThe Journal of Experimental Medicine, 2006
- Upstream and downstream of mTORGenes & Development, 2004
- TOR SignalingScience's STKE, 2003
- TCR engagement in the absence of cell cycle progression leads to T cell anergy independent of p27Kip1European Journal of Immunology, 2001