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

To better characterize human dendritic cells (DCs) that originate from lymp hoid 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 popu lation displayed high natural killer (NK) cell differentiation capacity whe n 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 (F L), granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor ne crosis factor (TNF)-alpha (standard condition), CD7(+)CD45RA(+) progenitors expanded less (37- vs 155-fold) but yielded a-fold higher CD1a(+) DC perce ntages than CD7(-)CD45RA(+) or CD7(+)CD45RA(-) progenitors. As reported for CD34(+)CD1a(-) thymocytes, cloning experiments demonstrated that CD7(+)CD4 5RA(+) cells comprised bipotent NK/DC progenitors. DCs differentiated from CD7(-)CD45RA(+) and CD7(+)CD45RA(+) progenitors differed as to E-cadherin C D123, CD116, and CD127 expression, but none of these was really discriminan t. Only CD7(+)CD45RA(+) or thymic progenitors differentiated into Lag(+)S10 0(+) Langerhans cells in the absence of exogenous transforming growth facto r (TGF)-beta1, Analysis of the DC differentiation pathways showed that CD7( +)CD45RA(+) progenitors generated CD1a(+)CD14(-) precursors that were macro - phage-colony stimulating factor (M-CSF) resistant and CD1a(-)CD14(+) prec ursors that readily differentiated into DCs under the standard condition, A ccordingly, CD7(+)CD45RA(+) progenitor-derived mature DCs produced 2- to 4- fold more IL-6, IL-12, and TNF-alpha on CD40 ligation and elicited 3- to 6- fold higher allogeneic T-lymphocyte reactivity than CD7(-)CD45RA(+) progeni tor-derived DCs, Altogether, these findings provide evidence that the DCs t hat differentiate from cord blood CD34(+)CD7(+)CD45RA(+) progenitors repres ent an original population for their developmental pathways and function. ( C) 2000 by The American Society of Hematology.