Expression pattern of Notch1, 2 and 3 and Jagged1 and 2 in lymphoid and stromal thymus components: distinct ligand-receptor interactions in intrathymic T cell development

The suggested role of Notch1 or its mutants in thymocyte differentiation an d T cell tumorigenesis raises the question of how the different members of the Notch family influence distinct steps in T cell development and the rol e played by Notch ligands in the thymus, We report here that different Notc h receptor-ligand partnerships may occur inside the thymus, as we observed differential expression of Notch1, 2 and 3 receptors, their ligands Jagged1 and 2, and downstream intracellular effecters hairy and Enhancer of Spill homolog 1 (HES-1) and hairy and Enhancer of Split homolog 5 (HES-5), depend ing on ontogenetic stage and thymic cell populations. Indeed, while Jagged2 is expressed in both stromal cells and thymocytes, Jagged1 expression is r estricted to stromal cells. Moreover, a differential distribution of Notch3 , with respect to Notch1, was observed in distinct age-related thymocyte su bsets. Finally, Notch3 was preferentially up-regulated in thymocytes, follo wing the induction of their differentiation by interaction with thymic epit helial cells expressing the cognate Jagged1 and 2 ligands, suggesting that, besides Notch1, Notch3 may also be involved in distinct steps of thymocyte development. Our results suggest that the Notch signaling pathway is invol ved in a complex interplay of T cell developmental stages, as a consequence of the heterogeneity and specific expression of members of the Notch recep tor family and their cognate ligands, in distinct thymic cell compartments.