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

V Cerovic, S A Houston, J Westlund, L Utriainen, E S Davison, C L Scott, C C Bain, T Joeris, W W Agace, R A Kroczek, A M Mowat, U Yrlid, S W F Milling

Research output: Contribution to journalArticlepeer-review

Abstract

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-tOVA 232-4 mice, which express ovalbumin in small intestinal epithelial cells (IECs). Among lymph DCs (LDCs) only CD103(+) CD11b(-) CD8α(+) 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(+) MHCII(hi) CD8α(+) migratory DCs, but absent from all other subsets, including the resident CD8α(hi) DCs. Crucially, delivery of purified CD8α(+) LDCs, but not other LDC subsets, into the MLN subcapsular lymphatic sinus induced proliferation of ovalbumin-specific, gut-tropic CD8(+) T cells in vivo. Finally, in 232-4 mice treated with R848, CD8α(+) LDCs were uniquely able to cross-prime interferon γ-producing CD8(+) T cells and drive their migration to the intestine. Our results clearly demonstrate that migrating CD8α(+) 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.

Original languageEnglish
Pages (from-to)38-48
Number of pages11
JournalMucosal Immunology
Volume8
Issue number1
DOIs
Publication statusPublished - Jan 2015

Fingerprint

Dive into the research topics of 'Lymph-borne CD8α+ dendritic cells are uniquely able to cross-prime CD8+ T cells with antigen acquired from intestinal epithelial cells'. Together they form a unique fingerprint.

Cite this