Peyer's patch dendritic cells process viral antigen from apoptotic epithelial cells in the intestine of reovirus-infected mice.

Fleeton MN, Contractor N, Leon F, Wetzel JD, Dermody TS, Kelsall BL
J Exp Med. 2004 200 (2): 235-45

PMID: 15263030 · PMCID: PMC2212021 · DOI:10.1084/jem.20041132

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 (sigma1) and nonstructural (sigmaNS) proteins in PPs of T1L-infected mice. Cells in the follicle-associated epithelium contained both sigma1 and sigmaNS, indicating productive viral replication. In contrast, sigma1, but not sigmaNS, was detected in the subepithelial dome (SED) in association with CD11c(+)/CD8alpha(-)/CD11b(lo) DCs, suggesting antigen uptake by these DCs in the absence of infection. Consistent with this possibility, PP DCs purified from infected mice contained sigma1, but not sigmaNS, and PP DCs from uninfected mice could not be productively infected in vitro. Furthermore, sigma1 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 CD8alpha(-)/CD11b(lo) 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.

MeSH Terms (22)

Animals Antigens, Viral Apoptosis CD4-Positive T-Lymphocytes CD8 Antigens CD11b Antigen CD11c Antigen Cell Division Cell Line Dendritic Cells Epithelial Cells Female Immunity, Mucosal Intestinal Mucosa Intestines Keratins Mice Mice, Inbred BALB C Microscopy, Confocal Microscopy, Fluorescence Orthoreovirus, Mammalian Peyer's Patches

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