Characterization of dendritic cell differentiation pathways from cord blood CD34+CD7+CD45RA+hematopoietic progenitor cells
Autor: | Micael Yagello, Edmond Kahn, Christian Schmitt, A H Dalloul, Bruno Canque, Jean Claude Gluckman, Colette Dezutter-Dambuyant, Sandrine Camus, Daniel Schmitt |
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Rok vydání: | 2000 |
Předmět: |
education.field_of_study
Population Immunology Stem cell factor chemical and pharmacologic phenomena hemic and immune systems Dendritic cell Dendritic cell differentiation Cell Biology Hematology Biology Molecular biology Biochemistry Natural killer cell Haematopoiesis medicine.anatomical_structure hemic and lymphatic diseases medicine Lymphopoiesis Progenitor cell education |
Zdroj: | Blood. 96:3748-3756 |
ISSN: | 1528-0020 0006-4971 |
DOI: | 10.1182/blood.v96.12.3748.h8003748_3748_3756 |
Popis: | 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) |
Databáze: | OpenAIRE |
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