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

Journal article
Authors V Cerovic
S A Houston
Jessica Westlund
L Utriainen
E S Davison
C L Scott
C C Bain
T Joeris
W W Agace
R A Kroczek
A M Mowat
Ulf Yrlid
S Wf Milling
Published in Mucosal immunology
Volume 8
Pages 38-48
ISSN 1935-3456
Publication year 2015
Published at Institute of Biomedicine, Department of Microbiology and Immunology
Pages 38-48
Language en
Links dx.doi.org/10.1038/mi.2014.40
Subject categories Basic Medicine, Immunobiology

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.Mucosal Immunology advance online publication, 21 May 2014; doi:10.1038/mi.2014.40.

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