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

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.

DOI: 10.4049/jimmunol.0803364

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@article{Qiu2009NovelSO, title={Novel subset of CD8\{alpha\}+ dendritic cells localized in the marginal zone is responsible for tolerance to cell-associated antigens.}, author={Chun-Hong Qiu and Yasunobu Miyake and Hitomi Kaise and Hiroshi Kitamura and Osamu Ohara and Masato Tanaka}, journal={Journal of immunology}, year={2009}, volume={182 7}, pages={4127-36} }