TY - JOUR
T1 - Vaccination with Plasmid DNA Activates Dendritic Cells via Toll-Like Receptor 9 (TLR9) but Functions in TLR9-Deficient Mice
AU - Spies, Barbara
AU - Hochrein, Hubertus
AU - Vabulas, Martin
AU - Huster, Katharina
AU - Busch, Dirk H.
AU - Schmitz, Frank
AU - Heit, Antje
AU - Wagner, Hermann
PY - 2003/12/1
Y1 - 2003/12/1
N2 - We analyzed whether the immunobiology of vaccinating plasmid DNA containing a transcription unit for OVA is influenced by immunostimulatory CpG motifs in the plasmid backbone. Indeed, plasmid DNA differentially activated in vitro myeloid and plasmacytoid dendritic cells (DCs) provided they expressed the CpG-DNA receptor, Toll-like receptor 9 (TLR9). Dependent on the DC subset, activation resulted in type 1 IFN production, while both DC subsets produced IL-6 and up-regulated expression of costimulatory molecules CD40 and CD86. In vivo, however, even upon repeated vaccination with plasmid DNA, priming of OVA-specific CTL and clonal expansion of SIINFEKL-specific CD8 T cells were equal in TLR9-positive and TLR9- or MyD88-negative mice. Overall, these results negate a dominant role of CpG-DNA/TLR9 interactions in long-term vaccination protocols.
AB - We analyzed whether the immunobiology of vaccinating plasmid DNA containing a transcription unit for OVA is influenced by immunostimulatory CpG motifs in the plasmid backbone. Indeed, plasmid DNA differentially activated in vitro myeloid and plasmacytoid dendritic cells (DCs) provided they expressed the CpG-DNA receptor, Toll-like receptor 9 (TLR9). Dependent on the DC subset, activation resulted in type 1 IFN production, while both DC subsets produced IL-6 and up-regulated expression of costimulatory molecules CD40 and CD86. In vivo, however, even upon repeated vaccination with plasmid DNA, priming of OVA-specific CTL and clonal expansion of SIINFEKL-specific CD8 T cells were equal in TLR9-positive and TLR9- or MyD88-negative mice. Overall, these results negate a dominant role of CpG-DNA/TLR9 interactions in long-term vaccination protocols.
UR - http://www.scopus.com/inward/record.url?scp=0345447639&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.171.11.5908
DO - 10.4049/jimmunol.171.11.5908
M3 - Article
C2 - 14634101
AN - SCOPUS:0345447639
SN - 0022-1767
VL - 171
SP - 5908
EP - 5912
JO - Journal of Immunology
JF - Journal of Immunology
IS - 11
ER -