Integrating canonical and metabolic signalling programmes in the regulation of T cell responses

Nat Rev Immunol. 2014 Jul;14(7):435-46. doi: 10.1038/nri3701.


Over the past decade, our understanding of T cell activation, differentiation and function has markedly expanded, providing a greater appreciation of the signals and pathways that regulate these processes. It has become clear that evolutionarily conserved pathways that regulate stress responses, metabolism, autophagy and survival have crucial and specific roles in regulating T cell responses. Recent studies suggest that the metabolic pathways involving MYC, hypoxia-inducible factor 1α (HIF1α), AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) are activated upon antigen recognition and that they are required for directing the consequences of T cell receptor engagement. The purpose of this Review is to provide an integrated view of the role of these metabolic pathways and of canonical T cell signalling pathways in regulating the outcome of T cell responses.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • AMP-Activated Protein Kinases / immunology
  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Differentiation / immunology*
  • Glycolysis
  • Hypoxia-Inducible Factor 1, alpha Subunit / immunology
  • Immunologic Memory / immunology
  • Lymphocyte Activation / immunology*
  • Mice
  • Proto-Oncogene Proteins c-myc / immunology
  • Receptors, Antigen, T-Cell / immunology
  • Signal Transduction / immunology
  • T-Lymphocytes, Helper-Inducer / immunology*
  • T-Lymphocytes, Helper-Inducer / metabolism
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism
  • TOR Serine-Threonine Kinases / immunology


  • Hif1a protein, mouse
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Myc protein, mouse
  • Proto-Oncogene Proteins c-myc
  • Receptors, Antigen, T-Cell
  • TOR Serine-Threonine Kinases
  • mTOR protein, mouse
  • AMP-Activated Protein Kinases