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

doi:https://doi.org/10.1038/ni.3027

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 journal › Article › Academic › peer-review

90 Citations (Scopus)

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 language	English
Pages (from-to)	1143-1151
Journal	Nature immunology
Volume	15
Issue number	12
DOIs	https://doi.org/10.1038/ni.3027
Publication status	Published - 2014

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https://doi.org/10.1038/ni.3027

Cite this

Backer, R. A., Helbig, C., Gentek, R., Kent, A., Laidlaw, B. J., Dominguez, C. X., de Souza, Y. S., van Trierum, S. E., van Beek, R., Rimmelzwaan, G. F., ten Brinke, A., Willemsen, A. M., van Kampen, A. H. C., Kaech, S. M., Blander, J. M., van Gisbergen, K., & Amsen, D. (2014). A central role for Notch in effector CD8(+) T cell differentiation. Nature immunology, 15(12), 1143-1151. https://doi.org/10.1038/ni.3027

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title = "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",

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

year = "2014",

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language = "English",

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Backer, RA, Helbig, C, Gentek, R, Kent, A, Laidlaw, BJ, Dominguez, CX, de Souza, YS, van Trierum, SE, van Beek, R, Rimmelzwaan, GF, ten Brinke, A, Willemsen, AM, van Kampen, AHC, Kaech, SM, Blander, JM, van Gisbergen, K & Amsen, D 2014, 'A central role for Notch in effector CD8(+) T cell differentiation', Nature immunology, vol. 15, no. 12, pp. 1143-1151. https://doi.org/10.1038/ni.3027

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AU - Backer, Ronald A.

AU - Helbig, Christina

AU - Gentek, Rebecca

AU - Kent, Andrew

AU - Laidlaw, Brian J.

AU - Dominguez, Claudia X.

AU - de Souza, Yevan S.

AU - van Trierum, Stella E.

AU - van Beek, Ruud

AU - Rimmelzwaan, Guus F.

AU - ten Brinke, Anja

AU - Willemsen, A. Marcel

AU - van Kampen, Antoine H. C.

AU - Kaech, Susan M.

AU - Blander, J. Magarian

AU - van Gisbergen, Klaas

AU - Amsen, Derk

PY - 2014

Y1 - 2014

N2 - 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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