Lymph-borne CD8α+ dendritic cells are uniquely able to cross-prime CD8+ T cells with antigen acquired from intestinal epithelial cells

Cross-presentation of cellular antigens is crucial for priming CD8(+) T cells, and generating immunity to intracellular pathogens-particularly viruses. It is unclear which intestinal phagocytes perform this function in vivo. To address this, we examined dendritic cells (DCs) from the intestinal lymph of IFABP-tOVA232-4 mice, which express ovalbumin in small intestinal epithelial cells (IECs). Among lymph DCs (LDCs) only CD103(+) CD11b(+) CD8 alpha(+) DCs cross-present IEC-derived ovalbumin to CD8(+) OT-I T cells. Similarly, in the mesenteric lymph nodes (MLNs), cross-presentation of IEC-ovalbumin was limited to the CD11c(+) MHCIIhi CD8 alpha(+) migratory DCs, but absent from all other subsets, including the resident CD8 alpha(hi) DCs. Crucially, delivery of purified CD8 alpha(+) LDCs, but not other LDC subsets, into the MLN subcapsular lymphatic sinus induced proliferation of ovalbumin-specific, gut-tropic CD8(+) Tcells in vivo. Finally, in 232-4 mice treated with R848, CD8 alpha(+) LDCs were uniquely able to cross-prime interferon gamma-producing CD8(+) Tcells and drive their migration to the intestine. Our results clearly demonstrate that migrating CD8 alpha(+) intestinal DCs are indispensable for cross-presentation of cellular antigens and, in conditions of inflammation, for the initial differentiation of effector CD8(+) T cells. They may therefore represent an important target for the development of antiviral vaccinations.