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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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Mucosal Immunology
volume
8
issue
1
pages
38 - 48
publisher
Nature Publishing Group
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  • pmid:24850430
  • wos:000346335600004
  • scopus:84926645140
ISSN
1933-0219
DOI
10.1038/mi.2014.40
language
English
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yes
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ed7b0318-086f-48b7-a888-500c740f9dca (old id 4452810)
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http://www.ncbi.nlm.nih.gov/pubmed/24850430?dopt=Abstract
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2014-06-04 23:46:13
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@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},
  volume       = {8},
  year         = {2015},
}