title: Stage-specific and differential notch dependency at the alphabeta and gammadelta T lineage bifurcation.
abstract: Signals transduced by Notch receptors are indispensable for T cell specification and differentiation of alphabeta T lineage cells. However, the role of Notch signals during alphabeta versus gammadelta T lineage decision remains controversial. Here, we addressed this question by employing a clonal analysis of CD4(-)CD8(-) (DN) progenitor potential to position the divergence of alphabeta and gammadelta T cell lineages to the late DN2 to DN3 developmental stages. Accordingly, alphabeta and gammadelta precursor frequencies within these T cell progenitor subsets were determined, both in the presence and absence of Notch signaling through Delta-like 1. Notch signals were found to be critical for the DN to CD4(+)CD8(+) (DP) transition, irrespective of the identity (pTalphabeta or gammadelta) of the inducing T cell receptor complex, whereas gammadelta T cells developed from gammadeltaTCR-expressing T cell progenitors in the absence of further Notch ligand interaction. Collectively, our findings demonstrate a differential, stage-specific requirement for Notch receptor-ligand interactions in the differentiation of alphabeta and gammadelta T cells from T cell progenitors.
authors.affiliation: Department of Immunology, University of Toronto, Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, Ontario M4N 3M5, Canada.
authors.forename: Maria
authors.initials: M
authors.lastname: Ciofani
authors.forename: Gisèle C
authors.initials: GC
authors.lastname: Knowles
authors.forename: David L
authors.initials: DL
authors.lastname: Wiest
authors.forename: Harald
authors.initials: H
authors.lastname: von Boehmer
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Zúñiga-Pflücker
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D018920:Coculture Techniques; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism; D008024:Ligands; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism*; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000378:metabolism
chemical_list: D008024:Ligands; D011948:Receptors, Antigen, T-Cell; D051880:Receptors, Notch