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

Mucosal Immunol. 2015 Jan;8(1):38-48. doi: 10.1038/mi.2014.40. Epub 2014 May 21.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens / immunology
  • CD8 Antigens / metabolism
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Movement / drug effects
  • Cell Movement / genetics
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Cross-Priming / drug effects
  • Cross-Priming / genetics
  • Dendritic Cells / immunology*
  • Imidazoles / administration & dosage
  • Imidazoles / pharmacology
  • Interferon-gamma / metabolism
  • Intestinal Mucosa / immunology
  • Lymph / immunology
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / genetics
  • Membrane Glycoproteins / agonists
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Ovalbumin / genetics
  • Ovalbumin / immunology
  • Ovalbumin / metabolism*
  • Toll-Like Receptor 7 / agonists


  • Antigens
  • CD8 Antigens
  • CD8alpha antigen
  • Imidazoles
  • Membrane Glycoproteins
  • Tlr7 protein, mouse
  • Toll-Like Receptor 7
  • Interferon-gamma
  • Ovalbumin
  • resiquimod