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Nat Immunol. 2005 Sep;6(9):881-8. Epub 2005 Jul 31.

Notch promotes survival of pre-T cells at the beta-selection checkpoint by regulating cellular metabolism.

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Department of Immunology, University of Toronto, Sunnybrook and Women's Research Institute, Toronto, Ontario M4N 3M5, Canada.


Notch signals are necessary for the functional outcomes of T cell receptor beta-selection, including differentiation, proliferation and rescue from apoptosis. The mechanism underlying this requirement for T cell development is unknown. Here we show that Notch receptor and Delta-like 1 ligand interactions promoted the survival of CD4(-)CD8(-) pre-T cells through the maintenance of cell size, glucose uptake and metabolism. Furthermore, the trophic effects of Notch signaling were mediated by the pathway of phosphatidylinositol-3-OH kinase and the kinase Akt, such that expression of active Atk overcame the requirement for Notch in beta-selection. Collectively, our results demonstrate involvement of Notch receptor-ligand interactions in the regulation of cellular metabolism, thus enabling the autonomous signaling capacity of the pre-T cell receptor complex.

[Indexed for MEDLINE]

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