Plasmacytoid dendritic cells mediate oral tolerance

Immunity. 2008 Sep 19;29(3):464-75. doi: 10.1016/j.immuni.2008.06.017.


Oral tolerance prevents oral sensitization to dietary antigens (Ags), including proteins and haptens, and development of delayed-type hypersensitivity (DTH) responses. We showed here that plasmacytoid dendritic cells (pDCs) prevented oral T cell priming and were responsible for systemic tolerance to CD4(+) and CD8(+) T cell-mediated DTH responses induced by Ag feeding. Systemic depletion of pDCs prevented induction of tolerance by antigen feeding. Transfer of oral Ag-loaded liver pDCs to naive recipient mice induced Ag-specific suppression of CD4(+) and CD8(+) T cell responses to protein and hapten, respectively. Liver is a site of oral Ag presentation, and pDCs appeared to induce anergy or deletion of Ag-specific T cells in the liver relatively rapidly via a CD4(+) T cell-independent mechanism. These data demonstrate that oral tolerance relies on Ag presentation by pDC to T cells and suggest that pDC could represent a key therapeutic target for intestinal and systemic inflammatory diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Dinitrofluorobenzene / immunology
  • Female
  • Hypersensitivity, Delayed / immunology*
  • Hypersensitivity, Delayed / metabolism
  • Immune Tolerance*
  • Liver / immunology
  • Lymph Nodes / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mouth Mucosa / immunology*
  • Spleen / immunology


  • Dinitrofluorobenzene