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The Journal of Immunology, 2004, 172: 7485-7494.
Copyright © 2004 by The American Association of Immunologists

Rat Plasmacytoid Dendritic Cells Are an Abundant Subset of MHC Class II+ CD4+CD11b–OX62– and Type I IFN-Producing Cells That Exhibit Selective Expression of Toll-Like Receptors 7 and 9 and Strong Responsiveness to CpG1

Francois-Xavier Hubert, Cécile Voisine2, Cédric Louvet2, Michèle Heslan and Régis Josien3

Institut National de la Santé et de la Recherche Médicale, Unité 437, and Institut de Transplantation et de Recherche en Transplantation, Nantes, France

We have identified in the rat a new subset of MHC class II+ CD4+CD3–CD11b– leukocytes that produce high amounts of type I IFN upon viral stimulation and that appeared homologous to plasmacytoid DC (pDC) previously described in humans and mice. These cells exhibited the following phenotype: CD5+,CD90+,CD45R+,CD45RC+,CD11c–,CD161a+,CD200+,CD172a+,CD32+,CD86+. Rat pDC did not express the DC-specific marker OX62 and were more abundant in the spleen than the classical CD4+ and CD4– subsets of OX62+CD11b+ DC we previously described that produced very little, if any, type I IFN. Spleen pDC exhibited an undifferentiated morphology and rapidly died in vitro, but showed extensive dendrite formation, survival, maturation, and moderate type I IFN production upon stimulation by oligonucleotides containing type B CpG motifs (CpG ODN). Type A CpG ODN and CD40 ligand induced pDC to produce large amounts of type I IFN, but did not promote maturation. CpG ODN and CD40 ligand, but not influenza virus, induced IL-12p40 and IL-6 secretion. Spleen pDC did not produce IL-12p70, TNF-{alpha}, IL-1{beta}, or IL-10 using these stimulation conditions. Correlating with their strong responsiveness to virus and CpG ODN, rat pDC specifically expressed Toll-like receptor 7 and 9 mRNA. Fresh spleen pDC were poor stimulators of allogenic CD4+ and CD8+ T cells, but became potent inducers of allogenic T cell proliferation as well as Th1 differentiation after stimulation by type B CpG. Therefore, rat pDC appear very similar to human pDC, indicating that the specific phenotype and functions of pDC have been highly conserved between species.




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