The mammalian target of rapamycin: linking T cell differentiation, function, and metabolism.
In the two-signal model of T cell activation, the outcome of antigen recognition is determined by the integration of multiple cues in the immune microenvironment. mTOR is an evolutionarily conserved PI3-kinase family member that plays a central role in integrating environmental cues in the form of amino acids, energy, and growth factors. Recently, an increasingly important role for mTOR in directing T cell activation and differentiation has become apparent. Here we review recent findings demonstrating the ability of mTOR to interpret signals in the immune microenvironment and program the generation of CD4(+) effector versus regulatory T cells, the generation of CD8(+) effector versus memory cells, T cell trafficking, and T cell activation versus anergy. The key theme to emerge from these studies is that the central role of mTOR provides a direct link between T cell metabolism and function.
Powell
Jonathan D
JD
Sidney-Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Delgoffe
Greg M
GM
D056704:Adaptive Immunity; D000818:Animals; D002454:Cell Differentiation; D002465:Cell Movement; D006801:Humans; D007156:Immunologic Memory; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D011506:Proteins; D013601:T-Lymphocytes / Q000166:cytology / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases; D018417:Th1 Cells / Q000276:immunology; D014157:Transcription Factors / Q000502:physiology
C493245:CRTC2 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D046912:Multiprotein Complexes; D011506:Proteins; D014157:Transcription Factors; C546842:MTOR protein, human; D000076222:Mechanistic Target of Rapamycin Complex 1; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases