The CD8α+ dendritic cell is responsible for inducing peripheral self-tolerance to tissue-associated antigens

Gabrielle T. Belz, Georg M.N. Behrens, Chris M. Smith, Jacques F.A.P. Miller, Claerwen Jones, Kristina Lejon, C. Garrison Fathman, Scott N. Mueller, Ken Shortman, Francis R. Carbone, William R. Heath

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405 Citations (Scopus)

Abstract

We previously described a mechanism for the maintenance of peripheral self-tolerance. This involves the cross-presentation of tissue-associated antigens by a bone marrow-derived cell type that stimulates the proliferation and ultimate deletion of self-reactive CD8 T cells. This process has been referred to as cross-tolerance. Here, we characterize the elusive cell type responsible for inducing cross-tolerance as a CD8α dendritic cell (DC). To achieve this aim, transgenic mice were generated expressing yellow fluorescent protein (YFP) linked to CTL epitopes for ovalbumin and glycoprotein B (gB) of herpes simplex virus under the rat insulin promoter (RIP). Although tracking of YFP was inconclusive, the use of a highly sensitive gB-specific hybridoma that produced β-galactosidase on encounter with antigen, enabled detection of antigen presentation by cells isolated from the pancreatic lymph node. This showed that a CD11c+CD8α+ cell was responsible for cross-tolerance, the same DC subset as previously implicated in cross-priming. These data indicate that CD8α+ DCs play a critical role in both tolerance and immunity to cell-associated antigens, providing a potential mechanism by which cytotoxic T lymphocyte can be immunized to viral antigens while maintaining tolerance to self.

Original languageEnglish
Pages (from-to)1099-1104
Number of pages6
JournalJournal of Experimental Medicine
Volume196
Issue number8
DOIs
Publication statusPublished - 21 Oct 2002
Externally publishedYes

Keywords

  • Antigen presentation
  • CD8 T cells
  • Cross-presentation
  • Cross-tolerance
  • Dendritic cells

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