Cutting Edge: Thymic Crosstalk Regulates Delta-Like 4 Expression on Cortical Epithelial Cells

• Published in: The Journal of immunology (1950) 2008-12, Vol.181 (12), p.8199-8203
• Main Authors: Fiorini, Emma, Ferrero, Isabel, Merck, Estelle, Favre, Stephanie, Pierres, Michel, Luther, Sanjiv A, MacDonald, H. Robson
• Format: Article
• Language: English
• Subjects: Animals; Animals, Newborn; Cell Communication - genetics; Cell Communication - immunology; Down-Regulation - immunology; Epithelial Cells - immunology; Epithelial Cells - metabolism; Intracellular Signaling Peptides and Proteins - antagonists & inhibitors; Intracellular Signaling Peptides and Proteins - genetics; Lymphopoiesis - genetics; Lymphopoiesis - immunology; Male; Membrane Proteins - antagonists & inhibitors; Membrane Proteins - biosynthesis; Membrane Proteins - genetics; Mice; Mice, Inbred C57BL; Mice, Knockout; Models, Immunological; Rats; Receptor, Notch1 - physiology; Stromal Cells - cytology; Stromal Cells - immunology; Stromal Cells - metabolism; Thymus Gland - cytology; Thymus Gland - embryology; Thymus Gland - immunology; Thymus Gland - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.181.12.8199

Interactions between Notch1 receptors on lymphoid progenitors and Delta-like 4 (DL4) ligands on cortical thymic epithelial cells (cTEC) are essential for T cell lineage commitment, expansion, and maturation in the thymus. Using a novel mAb against DL4, we show that DL4 levels on cTEC are very high in the fetal and neonatal thymus when thymocyte expansion is maximal but decrease dramatically in the adult when steady-state homeostasis is attained. Analysis of mutant mouse strains where thymocyte development is blocked at different stages indicates that lymphostromal interactions ("thymus crosstalk") are required for DL4 down-regulation on cTEC. Reconstitution of thymocyte development in these mutant mice further suggests that maturation of thymocytes to the CD4(+)CD8(+) stage and concomitant expansion are needed to promote DL4 down-regulation on cTEC. Collectively, our data support a model where thymic crosstalk quantitatively regulates the rate of Notch1-dependent thymopoiesis by controlling DL4 expression levels on cTEC.