Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Nature immunology, 2014-12, Vol.15 (12), p.1143-1151

Ort / Verlag

United States

Erscheinungsjahr

2014

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.