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 effects.

Alix de La Coste (1) , Emmanuelle Six (2) , Nicolas Fazilleau (3) , Laurent Mascarell (1) , Nicolas Legrand (4) , Marie-Pierre Mailhé (1) , Ana Cumano (5) , Yacine Laâbi (5) , Antonio A Freitas (1)

1 Biologie des Populations Lymphocytaires
2 SMAC - Signalisation Moléculaire et Activation Cellulaire
3 Immunité Antivirale, Biothérapie et Vaccins
4 Immunobiology
5 Développement des Lymphocytes

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(+) alphabeta 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.

Domaines: Immunologie

Alix de La Coste, Emmanuelle Six, Nicolas Fazilleau, Laurent Mascarell, Nicolas Legrand, et al.. 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 effects.. Journal of Immunology, 2005, 174 (5), pp.2730-7. ⟨10.4049/jimmunol.174.5.2730⟩. ⟨pasteur-00019658⟩