DNA activates human immune cells through a CpG sequence-dependent manner

While bacterial DNA and cytosine-guanosine-dinucleotide-containing oligonuc leotides (CpG ODN) are well described activators of murine immune cells,the ir effect on human cells is inconclusive. We investigated their properties on human peripheral blood mononuclear cells (PBMC) and subsets thereof, suc h as purified monocytes, T and B cells. Here we demonstrate that bacterial DNA and CpG ODN induce proliferation of B cells, while other subpopulations , such as monocytes and T cells, did not proliferate. PBMC mixed cell cultu res, as well as purified monocytes, produced interleukin-6 (IL-6), IL-12 an d tumour necrosis factor-cc upon stimulation with bacterial DNA; however, o nly IL-6 and IL-12 secretion became induced upon CpG ODN stimulation. We co nclude that monocytes, but not B or T cells, represent the prime source of cytokines. Monocytes up-regulated expression of antigen-presenting, major h istocompatibility complex class I and class II molecules in response to CpG DNA. In addition, both monocytes and B cells up-regulate costimulatory CD8 6 and CD40 molecules. The activation by CpG ODN depended on sequence motifs containing the core dinucleotide CG since destruction of the motif strongl y reduced immunostimulatory potential.