We explored the role of Peyer's patch (PP) dendritic cell (DC) populations in the induction of immune responses to reovirus strain type 1 Lang (T1L). Immunofluorescence staining revealed the presence of T1L structural (σ1) and nonstructural (σNS) proteins in PPs of T1L-infected mice. Cells in the follicle-associated epithelium contained both σ1 and σNS, indicating productive viral replication. In contrast, σ1, but not σNS, was detected in the subepithelial dome (SED) in association with CD11c+/CD8α−/CD11blo DCs, suggesting antigen uptake by these DCs in the absence of infection. Consistent with this possibility, PP DCs purified from infected mice contained σ1, but not σNS, and PP DCs from uninfected mice could not be productively infected in vitro. Furthermore, σ1 protein in the SED was associated with fragmented DNA by terminal deoxy-UTP nick-end labeling staining, activated caspase-3, and the epithelial cell protein cytokeratin, suggesting that DCs capture T1L antigen from infected apoptotic epithelial cells. Finally, PP DCs from infected mice activated T1L-primed CD4+ T cells in vitro. These studies show that CD8α−/CD11blo DCs in the PP SED process T1L antigen from infected apoptotic epithelial cells for presentation to CD4+ T cells, and therefore demonstrate the cross-presentation of virally infected cells by DCs in vivo during a natural viral infection.

The organized lymphoid tissues of the intestine likely play an important role in the balance between tolerance harmless mucosal Ags and commensal bacteria and immunity to mucosal pathogens. We examined the phenotype and function of plasmacytoid dendritic cells (pDCs) from murine Peyer’s patches (PPs). When stimulated with CpG-enriched oligodeoxynucleotides in vitro, PPs and spleen pDCs made equivalent levels of IL-12, yet PP pDCs were incapable of producing significant levels of type I IFNs. Three regulatory factors associated with mucosal tissues, PGE2, IL-10, and TGFβ, inhibited the ability of spleen pDCs to produce type I IFN in a dose-dependent fashion. These studies suggest that mucosal factors may regulate the production of type I IFN as well as IL-12 by pDCs. In the intestine, this may be beneficial in preventing harmful innate and adaptive immune responses to commensal microorganisms.