The role and regulation of mTOR in T-lymphocyte function

Arch Immunol Ther Exp (Warsz). 2012 Jun;60(3):173-81. doi: 10.1007/s00005-012-0171-4. Epub 2012 Apr 8.

Abstract

The conversion of naïve T cells into effector T cells is initiated by stimulation through the T-cell receptor (TCR). Upon activation, T cells undergo significant morphological and functional changes, putting new metabolic demands on the cell. Past research has identified the mammalian target of rapamycin (mTOR) as a critical regulator of cell metabolism, and the development of new genetic models has begun to reveal an important role for this pathway in the homeostasis and function of T lymphocytes. In this review, we focus on the most recent findings that demonstrate the ability of mTOR to regulate T-cell activation, CD8(+) memory cell formation and function, and helper T lineage differentiation. Furthermore, we highlight the importance of tight control of mTOR signaling by tuberous sclerosis complex 1 for T-cell homeostasis, and the regulation of mTOR signaling by diacylglycerol kinases and the RasGRP1-Ras-Erk1/2 pathway in the context of TCR signaling.

Publication types

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

MeSH terms

  • Animals
  • Cell Differentiation / immunology*
  • DNA-Binding Proteins / immunology
  • DNA-Binding Proteins / metabolism
  • Diacylglycerol Kinase / immunology
  • Diacylglycerol Kinase / metabolism
  • Guanine Nucleotide Exchange Factors / immunology
  • Guanine Nucleotide Exchange Factors / metabolism
  • Humans
  • Lymphocyte Activation / immunology*
  • MAP Kinase Signaling System / immunology
  • Mice
  • Receptors, Antigen, T-Cell / immunology
  • Signal Transduction / immunology*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • TOR Serine-Threonine Kinases / immunology*
  • TOR Serine-Threonine Kinases / metabolism
  • Tuberous Sclerosis Complex 1 Protein
  • Tumor Suppressor Proteins / immunology
  • Tumor Suppressor Proteins / metabolism

Substances

  • DNA-Binding Proteins
  • Guanine Nucleotide Exchange Factors
  • RASGRP1 protein, human
  • Receptors, Antigen, T-Cell
  • Tsc1 protein, mouse
  • Tuberous Sclerosis Complex 1 Protein
  • Tumor Suppressor Proteins
  • MTOR protein, human
  • Diacylglycerol Kinase
  • TOR Serine-Threonine Kinases