19265143

pubmed:Citation

6

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.

eng

AIM

MEDLINE

1550-6606

Electronic

182

Y

pubmed-meshheading:19265143-Animals, pubmed-meshheading:19265143-Antigen-Presenting Cells, pubmed-meshheading:19265143-Apoptosis, pubmed-meshheading:19265143-Cell Line, pubmed-meshheading:19265143-Cell Line, Transformed, pubmed-meshheading:19265143-Cell Movement, pubmed-meshheading:19265143-Cells, Cultured, pubmed-meshheading:19265143-Coculture Techniques, pubmed-meshheading:19265143-Cross-Priming, pubmed-meshheading:19265143-Dendritic Cells, pubmed-meshheading:19265143-Female, pubmed-meshheading:19265143-HLA-A2 Antigen, pubmed-meshheading:19265143-Humans, pubmed-meshheading:19265143-Mice, pubmed-meshheading:19265143-Mice, Inbred C57BL, pubmed-meshheading:19265143-Monocytes, pubmed-meshheading:19265143-Peptides, pubmed-meshheading:19265143-Phagocytosis, pubmed-meshheading:19265143-Protein Transport

MHC class I/peptide transfer between dendritic cells overcomes poor cross-presentation by monocyte-derived APCs that engulf dying cells.

Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural