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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Detalles Bibliográficos
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
Descripción
Sumario: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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