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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.

Cerovic, V ; Houston, S A ; Westlund, J ; Utriainen, L ; Davison, E S ; Scott, C L ; Bain, C C ; Joeris, Thorsten LU ; Agace, William LU and Kroczek, R A , et al. (2015) In Mucosal Immunology 8(1). p.38-48
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,... (More)
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. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Mucosal Immunology
volume
8
issue
1
pages
38 - 48
publisher
Nature Publishing Group
external identifiers
  • pmid:24850430
  • wos:000346335600004
  • scopus:84926645140
  • pmid:24850430
ISSN
1933-0219
DOI
10.1038/mi.2014.40
language
English
LU publication?
yes
id
ed7b0318-086f-48b7-a888-500c740f9dca (old id 4452810)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/24850430?dopt=Abstract
date added to LUP
2016-04-01 10:27:46
date last changed
2022-02-10 02:22:56
@article{ed7b0318-086f-48b7-a888-500c740f9dca,
  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.}},
  author       = {{Cerovic, V and Houston, S A and Westlund, J and Utriainen, L and Davison, E S and Scott, C L and Bain, C C and Joeris, Thorsten and Agace, William and Kroczek, R A and Mowat, A M and Yrlid, U and Milling, S Wf}},
  issn         = {{1933-0219}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{38--48}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Mucosal Immunology}},
  title        = {{Lymph-borne CD8α(+) dendritic cells are uniquely able to cross-prime CD8(+) T cells with antigen acquired from intestinal epithelial cells.}},
  url          = {{http://dx.doi.org/10.1038/mi.2014.40}},
  doi          = {{10.1038/mi.2014.40}},
  volume       = {{8}},
  year         = {{2015}},
}