Generation of interferon alpha-producing predendritic cell (Pre-DC)2 from human CD34(+) hematopoietic stem cells.
Upon viral stimulation, the natural interferon (IFN)-alpha/beta-producing cells (IPCs; also known as pre-dendritic cells (DCs 2) in human blood and peripheral lymphoid tissues rapidly produce huge amounts of IFN-alpha/beta. After performing this innate antiviral immune response, IPCs can differentiate into DCs and strongly stimulate T cell-mediated adaptive immune responses. Using four-color immunofluorescence flow cytometry, we have mapped the developmental pathway of pre-DC2/IPCs from CD34(+) hematopoietic stem cells in human fetal liver, bone marrow, and cord blood. At least four developmental stages were identified, including CD34(++)CD45RA(-) early progenitor cells, CD34(++)CD45RA(+) late progenitor cells, CD34(+)CD45RA(++)CD4(+)interleukin (IL)-3Ralpha(++) pro-DC2, and CD34(-)CD45RA(++) CD4(+)IL-3Ralpha(++) pre-DC2/IPCs. Pro-DC2s have already acquired the capacity to produce large amounts of IFN-alpha/beta upon viral stimulation and to differentiate into DCs in culture with IL-3 and CD40 ligand. CD34(++)CD45RA(-) early progenitor cells did not have the capacity to produce large amounts of IFN-alpha/beta in response to viral stimulation; however, they can be induced to undergo proliferation and differentiation into IPCs/pre-DC2 in culture with FLT3 ligand.
Blom
B
B
Department of Immunobiology, DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, California 94304, USA.
Ho
S
S
Antonenko
S
S
Liu
Y J
YJ
D018952:Antigens, CD34 / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000166:cytology; D023201:CD40 Ligand / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D005312:Fetal Blood / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D016130:Immunophenotyping; D016898:Interferon-alpha / Q000378:metabolism*; D007377:Interleukin-3 / Q000494:pharmacology; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000196:embryology; D008565:Membrane Proteins / Q000494:pharmacology; D013950:Thymus Gland / Q000166:cytology / Q000196:embryology; D013997:Time Factors; D014780:Viruses / Q000276:immunology
D018952:Antigens, CD34; D016898:Interferon-alpha; D007377:Interleukin-3; D008565:Membrane Proteins; C084881:flt3 ligand protein; D023201:CD40 Ligand