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; Emmanuelle Six; Nicolas Fazilleau; Laurent Mascarell; Nicolas Legrand; Marie-Pierre Mailhé; Ana Cumano; Yacine Laâbi; Antonio A Freitas

doi:10.4049/jimmunol.174.5.2730

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

J Immunol. 2005 Mar 1;174(5):2730-7. doi: 10.4049/jimmunol.174.5.2730.

Authors

Alix de La Coste¹, Emmanuelle Six, Nicolas Fazilleau, Laurent Mascarell, Nicolas Legrand, Marie-Pierre Mailhé, Ana Cumano, Yacine Laâbi, Antonio A Freitas

Affiliation

¹ Unité de Biologie des Populations Lymphocytaires, Centre National de la Recherche Scientifique, Unité de Recherche Associée 2582, Paris, France.

PMID: 15728481
DOI: 10.4049/jimmunol.174.5.2730

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adoptive Transfer
Animals
B-Lymphocytes / cytology
Bone Marrow Cells / cytology
Bone Marrow Cells / immunology
Bone Marrow Cells / metabolism
CD4 Antigens / biosynthesis
CD8 Antigens / biosynthesis
Cell Differentiation / genetics
Cell Differentiation / immunology
Cells, Cultured
Cytokines / biosynthesis
Fetus
Growth Inhibitors / biosynthesis
Growth Inhibitors / genetics
Growth Inhibitors / physiology
Hematopoietic Stem Cells / cytology
Hematopoietic Stem Cells / immunology
Hematopoietic Stem Cells / metabolism
Intracellular Signaling Peptides and Proteins
Ligands
Liver Transplantation / immunology
Membrane Proteins / biosynthesis*
Membrane Proteins / genetics*
Membrane Proteins / metabolism*
Membrane Proteins / physiology
Mice
Mice, Inbred C57BL
Mice, Nude
Receptors, Antigen, T-Cell, alpha-beta / biosynthesis
Receptors, Notch
Spleen / cytology
Spleen / immunology
Spleen / metabolism
T-Lymphocyte Subsets / cytology*
T-Lymphocyte Subsets / immunology
T-Lymphocyte Subsets / metabolism*
Thymus Gland / abnormalities*
Thymus Gland / immunology
Thymus Gland / metabolism

Substances

CD4 Antigens
CD8 Antigens
Cytokines
Growth Inhibitors
Intracellular Signaling Peptides and Proteins
Ligands
Membrane Proteins
Receptors, Antigen, T-Cell, alpha-beta
Receptors, Notch
delta protein