title: Notch1 deficiency dissociates the intrathymic development of dendritic cells and T cells.
abstract: Thymic dendritic cells (DCs) form a discrete subset of bone marrow (BM)-derived cells, the function of which is to mediate negative selection of autoreactive thymocytes. The developmental origin of thymic DCs remains controversial. Although cell transfer studies support a model in which T cells and thymic DCs develop from the same intrathymic pluripotential precursor, it remains possible that these two types of cells develop from independent intrathymic precursors. Notch proteins are cell surface receptors involved in the regulation of cell fate specification. We have recently reported that T cell development in inducible Notch1-deficient mice is severely impaired at an early stage, before the expression of T cell lineage markers. To investigate whether development of thymic DCs also depends on Notch1, we have constructed mixed BM chimeric mice. We report here that thymic DC development from Notch1(-/)- BM precursors is absolutely normal (in terms of absolute number and phenotype) in this competitive situation, despite the absence of Notch1(-/)- T cells. Furthermore, we find that peripheral DCs and Langerhans cells are also not affected by Notch1 deficiency. Our results demonstrate that the development of DCs is totally independent of Notch1 function, and strongly suggest a dissociation between intrathymic T cell and DC precursors.
authors.affiliation: Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, CH-1066 Epalinges, Switzerland. freddy.radtke@isrec.unil.ch
authors.forename: F
authors.initials: F
authors.lastname: Radtke
authors.forename: I
authors.initials: I
authors.lastname: Ferrero
authors.forename: A
authors.initials: A
authors.lastname: Wilson
authors.forename: R
authors.initials: R
authors.lastname: Lees
authors.forename: M
authors.initials: M
authors.lastname: Aguet
authors.forename: H R
authors.initials: HR
authors.lastname: MacDonald
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000166:cytology*; D006098:Granulocytes / Q000166:cytology; D006412:Hematopoietic Stem Cells / Q000166:cytology; D007694:Killer Cells, Natural / Q000166:cytology; D008264:Macrophages / Q000166:cytology; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D012107:Research Design; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology*; D014157:Transcription Factors
chemical_list: D008565:Membrane Proteins; C497762:Notch1 protein, mouse; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D014157:Transcription Factors