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 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)-alpha (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)-beta 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 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-alpha 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. (Blood. 2000;96:3748-3756)
Canque
B
B
E00-13 Institut National de la Recherche Scientifique (INSERM)- Université Paris 6, France. b_canque@club-internet.fr
Camus
S
S
Dalloul
A
A
Kahn
E
E
Yagello
M
M
Dezutter-Dambuyant
C
C
Schmitt
D
D
Schmitt
C
C
Gluckman
J C
JC
D000328:Adult; D018949:Antigens, CD1 / Q000097:blood; D018952:Antigens, CD34 / Q000097:blood; D019011:Antigens, CD7 / Q000097:blood; D002454:Cell Differentiation; D002648:Child; D016207:Cytokines / Q000187:drug effects; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D005312:Fetal Blood / Q000166:cytology* / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D006801:Humans; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology; D007801:Langerhans Cells / Q000166:cytology / Q000187:drug effects; D017493:Leukocyte Common Antigens / Q000097:blood; D018950:Lipopolysaccharide Receptors / Q000097:blood; D007959:Lymphocyte Culture Test, Mixed; D016131:Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D015398:Signal Transduction; D013950:Thymus Gland / Q000166:cytology; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D018949:Antigens, CD1; D018952:Antigens, CD34; D019011:Antigens, CD7; D016207:Cytokines; D018950:Lipopolysaccharide Receptors; D016212:Transforming Growth Factor beta; D017493:Leukocyte Common Antigens