Delta-like 4 is indispensable in thymic environment specific for T cell development

Hozumi, K. and Mailhos, C. and Negishi, N. and Hirano, K. and Yahata, T. and Ando, K. and Zuklys, S. and Holländer, G. A. and Shima, D. T. and Habu, S.. (2008) Delta-like 4 is indispensable in thymic environment specific for T cell development. Journal of experimental medicine, Vol. 205, H. 11. pp. 2507-2513.

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The thymic microenvironment is required for T cell development in vivo. However, in vitro studies have shown that when hematopoietic progenitors acquire Notch signaling via Delta-like (Dll)1 or Dll4, they differentiate into the T cell lineage in the absence of a thymic microenvironment. It is not clear, however, whether the thymus supports T cell development specifically by providing Notch signaling. To address this issue, we generated mice with a loxP-flanked allele of Dll4 and induced gene deletion specifically in thymic epithelial cells (TECs). In the thymus of mutant mice, the expression of Dll4 was abrogated on the epithelium, and the proportion of hematopoietic cells bearing the intracellular fragment of Notch1 (ICN1) was markedly decreased. Corresponding to this, CD4 CD8 double-positive or single-positive T cells were not detected in the thymus. Further analysis showed that the double-negative cell fraction was lacking T cell progenitors. The enforced expression of ICN1 in hematopoietic progenitors restored thymic T cell differentiation, even when the TECs were deficient in Dll4. These results indicate that the thymus-specific environment for determining T cell fate indispensably requires Dll4 expression to induce Notch signaling in the thymic immigrant cells.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Children's Hospital > Pediatric Immunology (Holländer)
UniBasel Contributors:Holländer, Georg
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Rockefeller University Press
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:31 Dec 2015 10:55
Deposited On:25 Apr 2014 08:00

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