International Immunology, Vol. 11, No. 7, 1017-1025,
July 1999
© 1999 Japanese Society for Immunology
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
1 Department of Experimental Medicine University of L'Aquila, Aquila 67100, Italy
2 Department of Experimental Medicine Pathology
3 Pasteur Institute Cenci-Bolognetti Foundation University La Sapienza' 00161 Rome, Italy
4 Institute of General Pathology University of Palermo 90134 Palermo, Italy
5 Institut de Biologie du Developpement (IBDM) Facultè díOdontologie (IMEB EA 2198)13288 Marseille, France
6 Howard Hughes Medical institute Department of Cell Biology,
Boyer Center for Molecular Medicine Yale University New Haven CT 0653 USA
7 Neurological Mediterranean Institute Neuromed 86077 Pozzilli (IS) Italy
8 Department of Cell Molecular Biology Karolinska Institute 5171-77 Stockholm, Sweden
Correspondence to: I. Screpanti, Department of Experimental Medicine and Pathology, University `La Sapienza', Viale Regina Elena 324, 00161 Rome, Italy
The suggested role of Notch1 or its mutants in thymocyte differentiation and T cell tumorigenesis raises the question of how the different members of the Notch family influence distinct steps in T cell development and the role played by Notch ligands in the thymus. We report here that different Notch 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 effectors hairy and Enhancer of Split homolog 1 (HES-1) and hairy and Enhancer of Split homolog 5 (HES-5), depending on ontogenetic stage and thymic cell populations. Indeed, while Jagged2 is expressed in both stromal cells and thymocytes, Jagged1 expression is restricted to stromal cells. Moreover, a differential distribution of Notch3, with respect to Notch1, was observed in distinct age-related thymocyte subsets. Finally, Notch3 was preferentially up-regulated in thymocytes, following the induction of their differentiation by interaction with thymic epithelial 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 involved in a complex interplay of T cell developmental stages, as a consequence of the heterogeneity and specific expression of members of the Notch receptor family and their cognate ligands, in distinct thymic cell compartments.
Keywords: cell–cell interaction, thymic stromal cells, thymocyte
The first two authors contribute equally to this work
Transmitting editor: L. Moretta
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|
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|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|