A Central Role for Notch in Effector CD8(+) T Cell Differentiation

Overview

Journal Nat Immunol

Date 2014 Oct 27

PMID 25344724

Citations 67

Authors

Ronald A Backer

Christina Helbig

Rebecca Gentek

Andrew Kent

Brian J Laidlaw

Claudia X Dominguez

Yevan S de Souza

Stella E van Trierum

Ruud van Beek

Guus F Rimmelzwaan

Anja Ten Brinke

A Marcel Willemsen

Antoine H C van Kampen

Susan M Kaech

J Magarian Blander

Klaas van Gisbergen

Derk Amsen

Affiliations

Soon will be listed here.

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.

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