Novel subset of CD8{alpha}+ dendritic cells localized in the marginal zone is responsible for tolerance to cell-associated antigens.
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.
Qiu
Chun-Hong
CH
RIKEN Research Center for Allergy and Immunology, Kanagawa, Japan.
Miyake
Yasunobu
Y
Kaise
Hitomi
H
Kitamura
Hiroshi
H
Ohara
Osamu
O
Tanaka
Masato
M
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D000954:Antigens, Surface / Q000276:immunology / Q000378:metabolism; D017209:Apoptosis / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology* / Q000378:metabolism; D002465:Cell Movement / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology; D020869:Gene Expression Profiling; D007108:Immune Tolerance; D007150:Immunohistochemistry; D039001:Integrin alpha Chains / Q000276:immunology / Q000378:metabolism; D037181:Lectins, C-Type / Q000276:immunology / Q000378:metabolism; D037241:Mannose-Binding Lectins / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D010587:Phagocytosis / Q000276:immunology; D013154:Spleen / Q000166:cytology* / Q000276:immunology
D015703:Antigens, CD; D000954:Antigens, Surface; D016827:CD8 Antigens; C431698:CD8alpha antigen; C498497:Cd207 protein, mouse; D039001:Integrin alpha Chains; D037181:Lectins, C-Type; D037241:Mannose-Binding Lectins; C091367:alpha E integrins