MHC class I/peptide transfer between dendritic cells overcomes poor cross-presentation by monocyte-derived APCs that engulf dying cells.
In vivo data suggest that monocytes participate critically in cross-presentation, but other data suggest that lymph node resident dendritic cells (DCs) mainly cross-present. Here, we utilized a three-dimensional model of a blood vessel wall that endogenously supports DC development from human monocytes, and we incorporated dying autologous cells in the subendothelial matrix of the model. Flu-infected dying cells promoted monocytes to become mature DCs and cross-present cell-associated Ags for the activation of CTLs. Similar responses were induced by loading the dying cells with the TLR7/8 ligand ssRNA, whereas dying cells loaded with TLR3 ligand were less efficient. Monocyte-derived DCs that developed in this model cross-presented Ag to T cells efficiently regardless of whether they engulfed detectable amounts of labeled dying cells. Unexpectedly, the monocyte-derived cells that directly engulfed dying cells in vitro were not the major APCs stimulating CD8(+) lymphocytes. Instead, bystander DCs acquired more robust capacity to cross-prime through receipt of MHC class I/peptide from the phagocytic, monocyte-derived cells. In mice, lymph node-homing monocyte-derived DCs processed Ags from engulfed cells and then transferred MHC class I/peptide complexes to confer cross-priming capacity to MHC class I-deficient lymph node resident CD8alpha(+) DCs. Thus, natural or synthetic TLR7/8 agonists contained within dying cells promote the conversion of monocytes to DCs with capacity for cross-presentation and for "cross-dressing" other DCs. These data reveal a way in which migratory monocyte-derived DCs and other DCs, like lymph node resident DCs, both mediate cross-presentation.
Qu
Chunfeng
C
Department of Gene and Cell Medicine and Institute for Immunology, Icahn Medical Institute, Mount Sinai School of Medicine, New York, NY 10029, USA.
Nguyen
Van Anh
VA
Merad
Miriam
M
Randolph
Gwendalyn J
GJ
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism; D017209:Apoptosis / Q000276:immunology*; D002460:Cell Line; D002461:Cell Line, Transformed; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D045142:Cross-Priming / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005260:Female; D015789:HLA-A2 Antigen / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D010455:Peptides / Q000276:immunology* / Q000378:metabolism; D010587:Phagocytosis / Q000276:immunology*; D021381:Protein Transport / Q000276:immunology
D015789:HLA-A2 Antigen; D010455:Peptides