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

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.

SUBMITTER: Backer RA

PROVIDER: S-EPMC4232996 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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

Backer Ronald A RA Helbig Christina C Gentek Rebecca R Kent Andrew A Laidlaw Brian J BJ Dominguez Claudia X CX de Souza Yevan S YS van Trierum Stella E SE van Beek Ruud R Rimmelzwaan Guus F GF ten Brinke Anja A Willemsen A Marcel AM van Kampen Antoine H C AH Kaech Susan M SM Blander J Magarian JM van Gisbergen Klaas K Amsen Derk D

Nature immunology 20141026 12

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 c ...[more]

PMID: 25344724

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

Publications

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

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