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

Upon viral stimulation, the natural interferon (IFN)-α/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-α/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)-3Rα⁺⁺ pro-DC2, and CD34⁻CD45RA⁺⁺ CD4⁺IL-3Rα⁺⁺ pre-DC2/IPCs. Pro-DC2s have already acquired the capacity to produce large amounts of IFN-α/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-α/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.