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PMID: 11120775 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Generation of interferon alpha-producing predendritic cell (Pre-DC)2 from human CD34(+) hematopoietic stem cells.

The Journal of experimental medicine ·Vol. 192 ·No. 12 ·2000-12-18 ·Pages 1785-96

Blom B, Ho S, Antonenko S, Liu YJ

Abstract

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.

MeSH Terms
Antigens, CD34/metabolism Bone Marrow Cells/cytology CD40 Ligand/pharmacology Cell Differentiation/drug effects Cell Division/drug effects Dendritic Cells/cytology,drug effects,immunology,metabolism Fetal Blood/cytology,drug effects,metabolism Flow Cytometry Hematopoietic Stem Cells/cytology,drug effects,immunology,metabolism Humans Immunophenotyping Interferon-alpha/metabolism Interleukin-3/pharmacology Leukocytes/cytology,drug effects,immunology,metabolism Liver/cytology,embryology Membrane Proteins/pharmacology Thymus Gland/cytology,embryology Time Factors Viruses/immunology
Chemicals
Antigens, CD34 Interferon-alpha Interleukin-3 Membrane Proteins flt3 ligand protein CD40 Ligand
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Blom B
Department of Immunobiology, DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, California 94304, USA.
Ho S
Antonenko S
Liu Y J
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.192.12.1785
Published
2000-12-18
Pages
1785-96
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2213503
Subset
IM
Corrections
CommentIn
PMID: 11120782
External Links
PubMed source DOI: 10.1084/jem.192.12.1785 PMC Full Text View journal details
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