The Notch receptor and its ligands are involved in many developmental proce
sses. They are highly expressed in the thymus and have been implicated in t
he CD4 versus CD8 lineage decision. We identified the constitutively active
intracellular fragment of murine Notch-1 as capable of rendering thymomas
resistant to glucocorticoid-induced apoptosis. This effect was confirmed in
other T cell lines and in CD4(+)CD8(+) DP thymocytes. Activation of the No
tch signaling pathway also upregulated a number of other markers that, like
steroid resistance, correlate with DP maturation into both the CD4 and CD8
lineages. These results suggest that Notch signaling is critically involve
d in the maturation of DP thymocytes into both CD4(+) and CD8(+) SP thymocy
tes.