A central role for Notch in effector CD8 + T cell differentiation Academic Article uri icon

Overview

MeSH Major

  • CD8-Positive T-Lymphocytes
  • Cell Differentiation
  • Receptors, Notch
  • T-Lymphocyte Subsets

abstract

  • Activated CD8(+) T cells choose between terminal effector cell (TEC) or memory precursor cell (MPC) fates. We found that the signaling receptor Notch controls this 'choice'. Notch promoted the differentiation of immediately protective TECs and was correspondingly required for the clearance of acute infection with influenza virus. Notch activated a major portion of the TEC-specific gene-expression program and suppressed the MPC-specific program. Expression of Notch was induced on naive CD8(+) T cells by inflammatory mediators and interleukin 2 (IL-2) via pathways dependent on the metabolic checkpoint kinase mTOR and the transcription factor T-bet. These pathways were subsequently amplified downstream of Notch, creating a positive feedback loop. Notch thus functions as a central hub where information from different sources converges to match effector T cell differentiation to the demands of an infection.

publication date

  • January 2014

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4232996

Digital Object Identifier (DOI)

  • 10.1038/ni.3027

PubMed ID

  • 25344724

Additional Document Info

start page

  • 1143

end page

  • 51

volume

  • 15

number

  • 12