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

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 Akt 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.