The Journal of Experimental Medicine
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Published 18 November 2002. doi:10.1084/jem.20021031
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© Rockefeller University Press, 0022-1007/2002/11/1307/ $5.00
The Journal of Experimental Medicine, Volume 196, Number 10, November 18, 2002 1307-1319

Mouse Plasmacytoid Cells : Long-lived Cells, Heterogeneous in Surface Phenotype and Function, that Differentiate Into CD8+ Dendritic Cells Only after Microbial Stimulus



Meredith O'Keeffe1, Hubertus Hochrein2, David Vremec1, Irina Caminschi1, Joanna L. Miller3, E. Margot Anders3, Li Wu1, Mireille H. Lahoud1, Sandrine Henri1, Bernadette Scott5, Paul Hertzog5, Lilliana Tatarczuch4 and Ken Shortman1

1 The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria 3050, Australia
2 Institute of Medical Microbiology, Immunology and Hygiene, Technical University of Munich, Munich, Germany
3 Department of Microbiology and Immunology, The University of Melbourne, Victoria 3010, Australia
4 Department of Veterinary Science, The University of Melbourne, Victoria 3010, Australia
5 Centre for Functional Genomics and Human Disease, Monash Institute of Reproduction and Development, Clayton, Victoria 3168, Australia

Address correspondence to Dr. Meredith O'Keeffe, The Walter and Eliza Hall Institute of Medical Research, P.O. Royal Melbourne Hospital, Victoria 3050, Australia. Phone: 61-3-9345-2533; Fax: 61-3-9347-0852; E-mail: okeeffe{at}wehi.edu.au

The CD45RAhiCD11cint plasmacytoid predendritic cells (p-preDCs) of mouse lymphoid organs, when stimulated in culture with CpG or influenza virus, produce large amounts of type I interferons and transform without division into CD8+CD205- DCs. P-preDCs express CIRE, the murine equivalent of DC-specific intercellular adhesion molecule 3 grabbing nonintegrin (DC-SIGN). P-preDCs are divisible by CD4 expression into two subgroups differing in turnover rate and in response to Staphylococcus aureus. The kinetics of bromodeoxyuridine labeling and the results of transfer to normal recipient mice indicate that CD4- p-preDCs are the immediate precursors of CD4+ p-preDCs. Similar experiments indicate that p-preDCs are normally long lived and are not the precursors of the short-lived steady-state conventional DCs. However, in line with the culture studies on transfer to influenza virus-stimulated mice the p-preDCs transform into CD8+CD205- DCs, distinct from conventional CD8+CD205+ DCs. Hence as well as activating preexistant DCs, microbial infection induces a wave of production of a new DC subtype. The functional implications of this shift in the DC network remain to be determined.

Key Words: plasmacytoid cells • dendritic cells • CD8 • CpG • microbial infection


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