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

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

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1
RIKEN Research Center for Allergy and Immunology, Kanagawa, Japan.

Abstract

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.

PMID:
19299710
DOI:
10.4049/jimmunol.0803364
[Indexed for MEDLINE]
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