The Journal of Experimental Medicine
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Published online 18 December 2000.
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© The Rockefeller University Press, 0022-1007/2000/12/1785/ $5.00
The Journal of Experimental Medicine, Volume 192, Number 12, December 18, 2000 1785-1796

Original Article

Generation of Interferon {alpha}–Producing Predendritic Cell (Pre-Dc)2 from Human Cd34+ Hematopoietic Stem Cells

Bianca Bloma, Stephen Hoa, Svetlana Antonenkoa, and Yong-Jun Liua

a Department of Immunobiology, DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, California 94304
Department of Immunobiology, DNAX Research Institute of Molecular and Cellular Biology, 901 California Ave., Palo Alto, CA 94304.650-496-1200650-496-1157

yliu{at}dnax.org

Upon viral stimulation, the natural interferon (IFN)-{alpha}/β–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}/β. 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)-3R{alpha}++ pro-DC2, and CD34–CD45RA++ CD4+IL-3R{alpha}++ pre-DC2/IPCs. Pro-DC2s have already acquired the capacity to produce large amounts of IFN-{alpha}/β 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}/β in response to viral stimulation; however, they can be induced to undergo proliferation and differentiation into IPCs/pre-DC2 in culture with FLT3 ligand.

Key Words: dendritic cells • interferon {alpha}/β–producing cells • stem cells • FLT3 ligand • interferon-producing cell

Abbreviations used in this paper: APC, allophycocyanin; DC, dendritic cell; FSC, forward scatter; HS, human serum; IPC, natural type 1 interferon-producing cell; LC, Langerhans cell; MNC, mononuclear cell; SCF, stem cell factor; SSC, side scatter.

© 2000 The Rockefeller University Press


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