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.
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.
de La Coste
Alix
A
Unité de Biologie des Populations Lymphocytaires, Centre National de la Recherche Scientifique, Unité de Recherche Associée 2582, Paris, France.
Six
Emmanuelle
E
Fazilleau
Nicolas
N
Mascarell
Laurent
L
Legrand
Nicolas
N
Mailhé
Marie-Pierre
MP
Cumano
Ana
A
Laâbi
Yacine
Y
Freitas
Antonio A
AA
D019264:Adoptive Transfer; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D015704:CD4 Antigens / Q000096:biosynthesis; D016827:CD8 Antigens / Q000096:biosynthesis; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D005333:Fetus; D006131:Growth Inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D016031:Liver Transplantation / Q000276:immunology; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis; D051880:Receptors, Notch; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D013950:Thymus Gland / Q000002:abnormalities* / Q000276:immunology / Q000378:metabolism
D015704:CD4 Antigens; D016827:CD8 Antigens; D016207:Cytokines; D006131:Growth Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D008565:Membrane Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D051880:Receptors, Notch; C064045:delta protein