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

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 i...

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Bibliographic Details
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
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Summary: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.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.181.12.8199