Journal
JOURNAL OF IMMUNOLOGY
Volume 182, Issue 7, Pages 4127-4136Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.0803364
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Funding
- Ministry of Education, Culture, Sports, Science and Technology in Japan
- Sankyo Foundation of Life Science
- Grants-in-Aid for Scientific Research [21790334] Funding Source: KAKEN
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Apoptotic cell clearance by dendritic cells (DCs) plays a crucial role in the maintenance of self-tolerance. In spleen, CD8 alpha(+) DCs are thought to be responsible for this phenomenon by phagocytosing circulating apoptotic cells. However, as CD8 alpha(+) 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 CD8 alpha(+) DCs responsible for tolerance induction to cell-associated Ags. Among splenic CD8 alpha(+) DCs, the CD103(+),CD207(+) subset was preferentially localized in the MZ and dominantly phagocytosed blood-borne apoptotic cells. After phagocytosis of apoptotic cells, this TIC 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, CD8 alpha(+) 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. The Journal of Immunology, 2009, 182: 4127-4136.
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