Novel subset of CD8{alpha}+ dendritic cells localized in the marginal zone is responsible for tolerance to cell-associated antigens

J Immunol. 2009 Apr 1;182(7):4127-36. doi: 10.4049/jimmunol.0803364.


Apoptotic cell clearance by dendritic cells (DCs) plays a crucial role in the maintenance of self-tolerance. In spleen, CD8alpha(+) DCs are thought to be responsible for this phenomenon by phagocytosing circulating apoptotic cells. However, as CD8alpha(+) DCs are believed to be predominantly localized in the T cell zone, it remains unclear how these DCs phagocytose blood-borne apoptotic cells accumulated in the marginal zone (MZ). In this study, we identified a subpopulation of CD8alpha(+) DCs responsible for tolerance induction to cell-associated Ags. Among splenic CD8alpha(+) DCs, the CD103(+),CD207(+) subset was preferentially localized in the MZ and dominantly phagocytosed blood-borne apoptotic cells. After phagocytosis of apoptotic cells, this DC subset migrated into the T cell zone for cross-presentation of cell-associated Ags. Stimulation of TLRs induced the disappearance of this DC subset. Consequently, CD8alpha(+) DCs neither phagocytosed injected apoptotic cells nor presented cell-associated Ags in mice treated with TLR ligands. Transient ablation of this DC subset by cytochrome c injection resulted in a failure of tolerance induction to cell-associated Ags, indicating that this DC subset is essential for tolerance induction by apoptotic cell clearance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation / immunology
  • Antigens, CD / immunology
  • Antigens, CD / metabolism
  • Antigens, Surface / immunology
  • Antigens, Surface / metabolism
  • Apoptosis / immunology
  • CD8 Antigens / immunology*
  • CD8 Antigens / metabolism
  • Cell Movement / immunology
  • Dendritic Cells / cytology*
  • Dendritic Cells / immunology*
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Gene Expression Profiling
  • Immune Tolerance*
  • Immunohistochemistry
  • Integrin alpha Chains / immunology
  • Integrin alpha Chains / metabolism
  • Lectins, C-Type / immunology
  • Lectins, C-Type / metabolism
  • Mannose-Binding Lectins / immunology
  • Mannose-Binding Lectins / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Oligonucleotide Array Sequence Analysis
  • Phagocytosis / immunology
  • Spleen / cytology*
  • Spleen / immunology


  • Antigens, CD
  • Antigens, Surface
  • CD8 Antigens
  • CD8alpha antigen
  • Cd207 protein, mouse
  • Integrin alpha Chains
  • Lectins, C-Type
  • Mannose-Binding Lectins
  • alpha E integrins