ACTIVATION OF CUTANEOUS DENDRITIC CELLS BY CPG-CONTAINING OLIGODEOXYNUCLEOTIDES - A ROLE FOR DENDRITIC CELLS IN THE AUGMENTATION OF TH1 RESPONSES BY IMMUNOSTIMULATORY DNA

Genetic vaccination depends at least in part on the adjuvant propertie s of plasmids, properties that have been ascribed to unmethylated CpG dinucleotides in bacterial DNA, Because dendritic cells (DC) participa te in the T cell priming that occurs during genetic vaccination, we re asoned that CpG-containing DNA might activate DC. Thus, we assessed th e effects of CpG oligodeoxynucleotides (CpG ODN) on Langerhans cell (L C)-like murine fetal skin-derived DC (FSDDC) in vitro and on LC in viv o. Treatment with CpG ODN as well as LPS induced FSDDC maturation, man ifested by decreased E-cadherin-mediated adhesion, up-regulation of MH C class II and costimulator molecule expression, and acquisition of en hanced accessory cell activity. In contrast to LPS, CpG ODN stimulated FSDDC to produce large amounts of IL-12 but only small amounts of IL- 6 and TNF-alpha. Injection of CpG ODN into murine dermis also led to e nhanced expression of MHC class II and CD86 Ag by LC in overlying epid ermis and intracytoplasmic IL-12 accumulation in a subpopulation of ac tivated LC, We conclude that immunostimulatory CpG ODN stimulate DC in vitro and in vivo. Bacterial DNA-based vaccines may preferentially el icit Th1-predominant immune responses because they activate and mobili ze DC and induce them to produce large amounts of IL-12.