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In Vivo and in Absence of a Thymus, the Enforced Expression of the Notch Ligands Delta-1 or Delta-4 Promotes T Cell Development with Specific Unique Effects¹

Alix de La Coste^*, Emmanuelle Six, Nicolas Fazilleau, Laurent Mascarell, Nicolas Legrand^2,*, Marie-Pierre Mailhé^*, Ana Cumano^¶, Yacine Laâbi^3,4,¶ and Antonio A. Freitas^4,5,*

^* Unité de Biologie des Populations Lymphocytaires, Unité de Biologie Moléculaire de l’Expression Génique, Centre National de la Recherche Scientifique, Unité de Recherche Associée 2582, Unité de Recherche et d’Expertise Immunité Anti-Virale, Biothérapie et Vaccins, Unité de Biologie des Régulations Immunitaires, and ^¶ Unité de Développement des Lymphocytes, Institut Pasteur, Paris, France

The role of Notch signaling in T cell commitment during lymphoid development is well established. However, the identity of the ligand that triggers this critical signal in vivo is still unclear. By overexpressing Delta-1 and Delta-4 ligands in the hemopoietic cells of athymic nu/nu host mice, we demonstrate that, in vivo and in the absence of a thymus, Delta-1 or Delta-4 expression is sufficient to promote T cell development from the most immature progenitor stages to complete maturation of both CD8⁺ and CD4⁺ T cells. The mature T cells developing in a Delta-1- or Delta-4-enriched environment express a diverse TCR repertoire, are able to proliferate upon in vitro TCR stimulation, but show different profiles of cytokine production after in vitro anti-CD3 stimulation.

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