CD8+ T lymphocytes producing high levels of interferon-gamma (IFN-gamma) and expressing antigen specific cytotoxic activity are effectively induced after plasmid DNA vaccination and mediate protection against several intracellular micro-organisms. Recent evidence suggests that the priming of CD8+ T-cell responses following DNA injection involves antigen presentation mediated by dendritic cells. Here, we show that bacterial DNA and synthetic oligonucleotides containing dinucleotide (CpG) motifs activate cytokine expression in dendritic cells and modulate in vivo CD8+ T-cell priming and differentiation.