PMID- 16537810
OWN - NLM
STAT- MEDLINE
DCOM- 20060822
LR  - 20210206
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 108
IP  - 2
DP  - 2006 Jul 15
TI  - Synergistic activation of dendritic cells by combined Toll-like receptor ligation 
      induces superior CTL responses in vivo.
PG  - 544-50
AB  - 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.
FAU - Warger, Tobias
AU  - Warger T
AD  - Institute for Immunology, Johannes Gutenberg University, Mainz, Germany.
FAU - Osterloh, Philipp
AU  - Osterloh P
FAU - Rechtsteiner, Gerd
AU  - Rechtsteiner G
FAU - Fassbender, Melanie
AU  - Fassbender M
FAU - Heib, Valeska
AU  - Heib V
FAU - Schmid, Beate
AU  - Schmid B
FAU - Schmitt, Edgar
AU  - Schmitt E
FAU - Schild, Hansjorg
AU  - Schild H
FAU - Radsak, Markus P
AU  - Radsak MP
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060314
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Ligands)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Myd88 protein, mouse)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (Tlr7 protein, mouse)
RN  - 0 (Toll-Like Receptor 3)
RN  - 0 (Toll-Like Receptor 7)
RN  - 0 (Toll-Like Receptors)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing/metabolism
MH  - Animals
MH  - Bone Marrow Cells
MH  - Dendritic Cells/*immunology/metabolism
MH  - Immunity
MH  - Ligands
MH  - Membrane Glycoproteins/immunology/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Myeloid Differentiation Factor 88
MH  - Signal Transduction
MH  - T-Lymphocytes
MH  - T-Lymphocytes, Cytotoxic/*immunology
MH  - T-Lymphocytes, Regulatory
MH  - Toll-Like Receptor 3/immunology/metabolism
MH  - Toll-Like Receptor 7/immunology/metabolism
MH  - Toll-Like Receptors/*immunology/metabolism
EDAT- 2006/03/16 09:00
MHDA- 2006/08/23 09:00
CRDT- 2006/03/16 09:00
PHST- 2006/03/16 09:00 [pubmed]
PHST- 2006/08/23 09:00 [medline]
PHST- 2006/03/16 09:00 [entrez]
AID - S0006-4971(20)52805-X [pii]
AID - 10.1182/blood-2005-10-4015 [doi]
PST - ppublish
SO  - Blood. 2006 Jul 15;108(2):544-50. doi: 10.1182/blood-2005-10-4015. Epub 2006 Mar 
      14.