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, Catherine L. Scott, C.C. Bain, Thorsten Joeris, William Winston Agace, R.A. Kroczek, A.M. Mowat, U. Yrlid, S.W.F. Milling

Research output: Contribution to journalJournal articleResearchpeer-review

69 Downloads (Pure)

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+ MHCIIhi CD8α+ migratory DCs, but absent from all other subsets, including the resident CD8αhi 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
JournalMucosal Immunology
Volume8
Issue number1
Pages (from-to)38-48
Number of pages11
ISSN1933-0219
DOIs
Publication statusPublished - 2015
Externally publishedYes

Bibliographical note

This work is licensed under the CreativeCommons Attribution-NonCommercial-No Derivative Works 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/

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

Cite this