Developmental origin of interferon-alpha-producing dendritic cells from hematopoietic precursors.
OBJECTIVE
The aim of this study was to determine the lineage origin of interferon-alpha-producing cells (IPCs), also called plasmacytoid dendritic cells, in mice by evaluating the ability of common lymphoid (CLP) and myeloid (CMP) progenitors to give rise to IPCs.


METHODS
Sublethally irradiated C57Bl/6 mice were intravenously transplanted with rigorously purified lymphoid and myeloid progenitors from a congenic mouse strain. At various time points posttransplantation mice were analyzed for donor-derived cells by flow cytometry. The developmental potential of all progenitor populations was also tested in in vitro cultures. In addition, in vitro and in vivo derived IPCs were functionally assessed for their interferon-alpha production after virus challenge.


RESULTS
Transplantation of 1 x 10(4) common myeloid progenitors, 1 x 10(4) common lymphoid progenitors or 2.5 x 10(4) granulocyte/macrophage progenitors all led to the generation of IPCs within 2 to 3 weeks. In general, IPC reconstitution in spleen and liver by CMPs was more efficient than by CLP. Adding Flt3L alone to in vitro cultures was sufficient to support the development of IPCs from myeloid progenitors whereas CLPs required additional survival factors provided either by stroma cells or by introduction of transgenic Bcl-2. Both myeloid- and lymphoid-derived IPC were indistinguishable by function, gene expression, and morphology.


CONCLUSIONS
Surprisingly, our results clearly show that murine IPCs differentiate from both lineages but are mainly of myeloid origin. These results extend to IPCs the observation made originally in classical dendritic cells that cellular expression of so called lineage markers does not correlate with lineal origin.
Karsunky
Holger
H
Department of Pathology, Stanford University School of Medicine, Stanford, Calif, USA. karsunky@stanford.edu
Merad
Miriam
M
Mende
Ines
I
Manz
Markus G
MG
Engleman
Edgar G
EG
Weissman
Irving L
IL
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology; D016898:Interferon-alpha / Q000235:genetics*; D007376:Interleukin-2 / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D033581:Stem Cell Transplantation; D019172:Transplantation Conditioning; D014916:Whole-Body Irradiation
D015703:Antigens, CD; D016898:Interferon-alpha; D007376:Interleukin-2; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger