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

Activated CD8(+) T cells choose between terminal effector cell (TEC) or memory precursor cell (MPC) fates. We show that Notch controls this choice. Notch promoted differentiation of immediately protective TECs and was correspondingly required for clearance of an acute influenza virus infection. Notc...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2014
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4232996/
https://www.ncbi.nlm.nih.gov/pubmed/25344724
http://dx.doi.org/10.1038/ni.3027
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author 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
author_facet 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
author_sort Backer, Ronald A.
collection PubMed
description Activated CD8(+) T cells choose between terminal effector cell (TEC) or memory precursor cell (MPC) fates. We show that Notch controls this choice. Notch promoted differentiation of immediately protective TECs and was correspondingly required for clearance of an acute influenza virus infection. Notch activated a major portion of the TEC-specific gene expression program and suppressed the MPC-specific program. Expression of Notch receptors was induced on naïve CD8(+) T cells by inflammatory mediators and interleukin 2 (IL-2) via mTOR and T-bet dependent pathways. 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 the infection.
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spelling pubmed-42329962015-06-01 A central role for Notch in effector CD8(+) T cell differentiation 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 Nat Immunol Article Activated CD8(+) T cells choose between terminal effector cell (TEC) or memory precursor cell (MPC) fates. We show that Notch controls this choice. Notch promoted differentiation of immediately protective TECs and was correspondingly required for clearance of an acute influenza virus infection. Notch activated a major portion of the TEC-specific gene expression program and suppressed the MPC-specific program. Expression of Notch receptors was induced on naïve CD8(+) T cells by inflammatory mediators and interleukin 2 (IL-2) via mTOR and T-bet dependent pathways. 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 the infection. 2014-10-26 2014-12 /pmc/articles/PMC4232996/ /pubmed/25344724 http://dx.doi.org/10.1038/ni.3027 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
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
A central role for Notch in effector CD8(+) T cell differentiation
title A central role for Notch in effector CD8(+) T cell differentiation
title_full A central role for Notch in effector CD8(+) T cell differentiation
title_fullStr A central role for Notch in effector CD8(+) T cell differentiation
title_full_unstemmed A central role for Notch in effector CD8(+) T cell differentiation
title_short A central role for Notch in effector CD8(+) T cell differentiation
title_sort central role for notch in effector cd8(+) t cell differentiation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4232996/
https://www.ncbi.nlm.nih.gov/pubmed/25344724
http://dx.doi.org/10.1038/ni.3027
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