Synergistic activation of dendritic cells by combined Toll-like receptor ligation induces superior CTL responses in vivo
Toll-like receptors (TLRs) are able to interact with pathogen-derived products and their signals induce the coordinated activation of innate and adaptive immune mechanisms. Dendritic cells (DCs) play a central role in these events. As the different TLRs are able to trigger MyD88/TRIF-dependent and -...
Gespeichert in:
Veröffentlicht in: | Blood 2006-07, Vol.108 (2), p.544-550 |
---|---|
Hauptverfasser: | , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
Zusammenfassung: | Toll-like receptors (TLRs) are able to interact with pathogen-derived products and their signals induce the coordinated activation of innate and adaptive immune mechanisms. Dendritic cells (DCs) play a central role in these events. As the different TLRs are able to trigger MyD88/TRIF-dependent and -independent signaling pathways, we wondered if the simultaneous activation of these signaling cascades would synergize with respect to DC activation and induce superior cytotoxic T-lymphocyte (CTL) activity in vivo. We observed that indeed the combined activation of MyD88-dependent and -independent signaling induced by TLR7 and TLR3 ligands provoked a more rapid and more sustained bone marrow–derived DC (BMDC) activation with regard to the secretion of proinflammatory cytokines, like IL-6 and IL-12p70, and the expression of costimulatory molecules like CD40, CD70, and CD86. Furthermore, in the presence of combined TLR ligand–stimulated DCs, CD4+ and CD8+ T cells were insensitive toward the inhibitory effects of regulatory T cells. Most importantly, peptide-loaded BMDCs stimulated by TLR ligand combinations resulted in a marked increase of CTL effector functions in wild-type mice in vivo. Thus, our results provide evidence that unlocking the full potential of DCs by advanced activation protocols will boost their immunogenic potential and improve DC-based vaccination strategies. |
---|---|
ISSN: | 0006-4971 1528-0020 |
DOI: | 10.1182/blood-2005-10-4015 |