A central role for Notch in effector CD8 + T cell differentiation

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

Research output: Contribution to journalArticlepeer-review

83 Scopus citations

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.

Original languageEnglish
Pages (from-to)1143-1151
Number of pages9
JournalNature immunology
Volume15
Issue number12
DOIs
StatePublished - Nov 18 2014

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