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 CpG.
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-1beta, 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.
Hubert
Francois-Xavier
FX
Institut National de la Santé et de la Recherche Médicale, Unité 437, 30 boulevard Jean Monnet, 44093 Nantes Cedex 1, France.
Voisine
Cécile
C
Louvet
Cédric
C
Heslan
Michèle
M
Josien
Régis
R
D000818:Animals; D000943:Antigens, Differentiation / Q000032:analysis*; D039481:CD11b Antigen / Q000032:analysis; D015704:CD4 Antigens / Q000032:analysis; D018899:CpG Islands / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000235:genetics; D003713:Dendritic Cells / Q000737:chemistry / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D016130:Immunophenotyping; D007370:Interferon Type I / Q000032:analysis / Q000096:biosynthesis*; D008213:Lymphocyte Activation; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000235:genetics*; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000166:cytology; D018418:Th2 Cells / Q000166:cytology; D051199:Toll-Like Receptor 7; D051217:Toll-Like Receptor 9
D000943:Antigens, Differentiation; D039481:CD11b Antigen; D015704:CD4 Antigens; D004268:DNA-Binding Proteins; D000949:Histocompatibility Antigens Class II; D007370:Interferon Type I; C459465:OX-62 antigen, rat; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C489639:TLR7 protein, rat; C489640:Tlr9 protein, rat; D051199:Toll-Like Receptor 7; D051217:Toll-Like Receptor 9