Identification and characterization of intestinal Peyer's patch interferon-α producing (Plasmacytoid) dendritic cells

Recently, a subset of murine dendritic cells (DC) has been identified that resembles human plasmacytoid (pDC) the principal interferon-alpha (IFN-alpha) producing cells in blood. In this study, C57BL/10 (B10;H2(b)) mice were treated with fins-like tyrosine 3 kinase Ligand (Flt3L; 10 mug/d; i.p.; 10 days) that expands DC selectively in vivo. Putative pDC (CD11c(+)B220(+)) were identified in the subepithelial dome and in interfollicular regions of intestinal Peyer's patches (PP) from both normal and Flt3L-treated animals. Freshly-isolated, immunobead-purified CD11c(+) DC from PP were flow-sorted to obtain lineage (CD11b(-)CD19(-)) CD11c(+) B220(+) DC (purity > 96%). Flow cytometric analysis revealed that these sorted PPpDC were negative for surface markers associated with myeloid DC (CD11b) and expressed only tow levels of the "lymphoid-related" DC marker CD8alphaalpha(+). They expressed low levels of costimulatory molecules and moderate MHC class II. They proved weak stimulators of naive allogeneic (C3H; H2(k)) T-cell proliferation. Cyto-spin preparations of sorted CD11c(+)B220(+) cells revealed plasmacytoid morphology similar to that of human pDC. Immunocytochemistry and enzyme immunoassay revealed that, within 24-hour culture with Herpes simplex virus (10 p.f.u./cell), a subpopulation of stimulated (but not unstimulated) CD11c(+)B220(+) DC produced and secreted IFN-alpha. This novel DC subset may play important roles in innate and adaptive immune responses of the gut and in the regulation of mucosal immune reactions.