Characterization of dendritic cell differentiation pathways from cord blood CD34+CD7+CD45RA+hematopoietic progenitor cells

B Canque, S Camus, A Dalloul, E Kahn… - Blood, The Journal …, 2000 - ashpublications.org
B Canque, S Camus, A Dalloul, E Kahn, M Yagello, C Dezutter-Dambuyant, D Schmitt…
Blood, The Journal of the American Society of Hematology, 2000ashpublications.org
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 …
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 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)-α (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)-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 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-α 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.
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