Affiliation:
1. 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.
Abstract
Abstract
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 CD7−CD45RA+ 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)-α (standard condition), CD7+CD45RA+ progenitors expanded less (37- vs 155-fold) but yielded 2-fold higher CD1a+ DC percentages than CD7−CD45RA+ 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 CD7−CD45RA+ 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)-β1. 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 CD1a−CD14+ 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-α on CD40 ligation and elicited 3- to 6-fold higher allogeneic T-lymphocyte reactivity than CD7−CD45RA+ 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.
Publisher
American Society of Hematology
Subject
Cell Biology,Hematology,Immunology,Biochemistry
Cited by
50 articles.
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