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

by van Kampen, Antoine H C , Gentek, Rebecca , Backer, Ronald A , van Gisbergen, Klaas , ten Brinke, Anja , van Beek, Ruud , Blander, J Magarian , Amsen, Derk , de Souza, Yevan S , Dominguez, Claudia X , Rimmelzwaan, Guus F , van Trierum, Stella E , Kaech, Susan M , Willemsen, A Marcel , Helbig, Christina , Kent, Andrew , Laidlaw, Brian J

in Influenza virus

2014

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

in Influenza virus

2014

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Journal Article

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

van Kampen, Antoine H C,

Gentek, Rebecca,

Backer, Ronald A,

van Gisbergen, Klaas,

ten Brinke, Anja,

van Beek, Ruud,

Blander, J Magarian,

Amsen, Derk,

de Souza, Yevan S,

Dominguez, Claudia X,

Rimmelzwaan, Guus F,

van Trierum, Stella E,

Kaech, Susan M,

Willemsen, A Marcel,

Helbig, Christina,

Kent, Andrew,

Laidlaw, Brian J

2014

Overview

Activated CD8 super(+) 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 super(+) 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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Subject

Influenza virus