Efficient chemokine-dependent migration and primary and secondary IL-12 secretion by human dendritic cells stimulated through Toll-like receptors.
Recent findings have demonstrated the properties of cell migration and cytokine secretion to be mutually exclusive and linked them to different functional subpopulations of dendritic cells (DCs). We studied human monocyte-derived DCs after stimulation with peptidoglycan (PGN), poly(I:C), lipopolysaccharide (LPS), and R848 (resiquimod) and found the resulting mature DCs to express CCR7, to migrate toward CCL19 and to be efficient primary interleukin (IL)-12 producers. Importantly, the potential for secondary production of large amounts of IL-12p70 in response to CD40 ligation was also preserved after stimulation by all Toll-like receptor (TLR) ligands. Differences between the TLR ligands were seen in the primary secretion of IL-12 and IL-23, in the survival of the DCs and in the expression of CD38. Finally, DCs stimulated by R848 were efficient in expanding peptide-specific CD8-positive T cells capable of peptide-specific target cell lysis. Together, our data suggest that TLR ligands induce the generation of mature DCs that integrate migratory and cytokine secretory capacity as well as cytotoxic T lymphocyte (CTL) stimulatory properties.
Lehner
Manfred
M
Department of Cellular Therapy, Children's University Hospital, Friedrich-Alexander University Erlangen-Nuernberg, Erlangen, Germany.
Morhart
Patrick
P
Stilper
Andrea
A
Petermann
Dagmar
D
Weller
Perdita
P
Stachel
Daniel
D
Holter
Wolfgang
W
D051997:ADP-ribosyl Cyclase 1 / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002465:Cell Movement; D054415:Chemokine CCL19; D018925:Chemokines / Q000276:immunology*; D019742:Chemokines, CC / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D018664:Interleukin-12 / Q000378:metabolism*; D053759:Interleukin-23 / Q000378:metabolism; D008024:Ligands; D008070:Lipopolysaccharides / Q000494:pharmacology; D010457:Peptidoglycan / Q000494:pharmacology; D051193:Toll-Like Receptors / Q000378:metabolism*
C515460:CCL19 protein, human; D054415:Chemokine CCL19; D018925:Chemokines; D019742:Chemokines, CC; D007093:Imidazoles; D053759:Interleukin-23; D008024:Ligands; D008070:Lipopolysaccharides; D010457:Peptidoglycan; D051193:Toll-Like Receptors; D018664:Interleukin-12; D051997:ADP-ribosyl Cyclase 1; C402365:resiquimod