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Related Collections Hematopoiesis and Stem Cells Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 December 2000, Vol. 96, No. 12, pp. 3748-3756 HEMATOPOIESIS Characterization of dendritic cell differentiation pathways from cord blood CD34+CD7+CD45RA+ hematopoietic progenitor cells Bruno Canque, Sandrine Camus, Ali Dalloul, Edmond Kahn, Micaël Yagello, Colette Dezutter-Dambuyant, Daniel Schmitt, Christian Schmitt, and Jean Claude Gluckman From E00-13 Institut National de la Recherche Scientifique (INSERM)- Université Paris 6, service d'Immunologie Biologique and laboratoire d'Immunologie Cellulaire et Immunopathologie de l'Ecole Pratique des Hautes Etudes; Laboratoire d'Immunologie Cellulaire, UMR7627 Centre National de la Recherche Scientifique; INSERM U494; hôpital de la Pitié-Salpêtrière, Paris; INSERM U346, hôpital Edouard Herriot, Lyon, France. To better characterize human dendritic cells (DCs) that originate from lymphoid progenitors, the authors examined the DC differentiation pathways from a novel CD7+CD45RA+ progenitor population found among cord blood CD34+ cells. Unlike CD7CD45RA+ and CD7+CD45RA progenitors, this population displayed high natural killer (NK) cell differentiation capacity when cultured with stem cell factor (SCF), interleukin (IL)-2, IL-7, and IL-15, attesting to its lymphoid potential. In cultures with SCF, Flt3 ligand (FL), granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor (TNF)- (standard condition), CD7+CD45RA+ progenitors expanded less (37- vs 155-fold) but yielded 2-fold higher CD1a+ DC percentages than CD7CD45RA+ or CD7+CD45RA progenitors. As reported for CD34+CD1a thymocytes, cloning experiments demonstrated that CD7+CD45RA+ cells comprised bipotent NK/DC progenitors. DCs differentiated from CD7CD45RA+ and CD7+CD45RA+ progenitors differed as to E-cadherin CD123, CD116, and CD127 expression, but none of these was really discriminant. Only CD7+CD45RA+ or thymic progenitors differentiated into Lag+S100+ Langerhans cells in the absence of exogenous transforming growth factor (TGF)-1. Analysis of the DC differentiation pathways showed that CD7+CD45RA+ progenitors generated CD1a+CD14 precursors that were macrophage-colony stimulating factor (M-CSF) resistant and CD1aCD14+ precursors that readily differentiated into DCs under the standard condition. Accordingly, CD7+CD45RA+ progenitor-derived mature DCs produced 2- to 4-fold more IL-6, IL-12, and TNF- on CD40 ligation and elicited 3- to 6-fold higher allogeneic T-lymphocyte reactivity than CD7CD45RA+ progenitor-derived DCs. Altogether, these findings provide evidence that the DCs that differentiate from cord blood CD34+CD7+CD45RA+ progenitors represent an original population for their developmental pathways and function. © 2000 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: I. Mende, H. Karsunky, I. L. Weissman, E. G. Engleman, and M. Merad Flk2+ myeloid progenitors are the main source of Langerhans cells Blood, February 15, 2006; 107(4): 1383 - 1390. [Abstract] [Full Text] [PDF] N. Hoshino, N. Katayama, T. Shibasaki, K. Ohishi, J. Nishioka, M. Masuya, Y. Miyahara, M. Hayashida, D. Shimomura, T. Kato, et al. A novel role for Notch ligand Delta-1 as a regulator of human Langerhans cell development from blood monocytes J. Leukoc. Biol., October 1, 2005; 78(4): 921 - 929. [Abstract] [Full Text] [PDF] R. Haddad, P. Guardiola, B. Izac, C. Thibault, J. Radich, A.-L. Delezoide, C. 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