T cell exit from quiescence and differentiation into Th2 cells depend on Raptor-mTORC1-mediated metabolic reprogramming

Immunity. 2013 Dec 12;39(6):1043-56. doi: 10.1016/j.immuni.2013.09.015. Epub 2013 Dec 5.


Naive T cells respond to antigen stimulation by exiting from quiescence and initiating clonal expansion and functional differentiation, but the control mechanism is elusive. Here we describe that Raptor-mTORC1-dependent metabolic reprogramming is a central determinant of this transitional process. Loss of Raptor abrogated T cell priming and T helper 2 (Th2) cell differentiation, although Raptor function is less important for continuous proliferation of actively cycling cells. mTORC1 coordinated multiple metabolic programs in T cells including glycolysis, lipid synthesis, and oxidative phosphorylation to mediate antigen-triggered exit from quiescence. mTORC1 further linked glucose metabolism to the initiation of Th2 cell differentiation by orchestrating cytokine receptor expression and cytokine responsiveness. Activation of Raptor-mTORC1 integrated T cell receptor and CD28 costimulatory signals in antigen-stimulated T cells. Our studies identify a Raptor-mTORC1-dependent pathway linking signal-dependent metabolic reprogramming to quiescence exit, and this in turn coordinates lymphocyte activation and fate decisions in adaptive immunity.

Publication types

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

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Cell Cycle
  • Cell Differentiation*
  • Cell Proliferation
  • Cells, Cultured
  • Cytokines / metabolism
  • Gene Deletion
  • Glucose / metabolism
  • Lymphocyte Activation / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Regulatory-Associated Protein of mTOR
  • Signal Transduction
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / immunology*
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism*
  • Th2 Cells / cytology*


  • Adaptor Proteins, Signal Transducing
  • Cytokines
  • Regulatory-Associated Protein of mTOR
  • Rptor protein, mouse
  • TOR Serine-Threonine Kinases
  • Glucose

Associated data

  • GEO/GSE51668