Poly-guanosine motifs costimulate antigen-reactive CD8 T cells while bacterial CpG-DNA affect T-cell activation via antigen-presenting cell-derived cytokines

Pathogen-derived pattern recognition ligands like lipopolysaccharide (LPS) and bacterial cytidine-guanosine (CpG)-DNA not only activate dendritic cell s and macrophages but are also mitogenic for B cells. Less clear are the cl aimed effects of CpG-DNA on T cells, which range from direct activation, co stimulation, or indirect transient activation via antigen-presenting cell ( APC)-derived interferon type I (IFN type I). Here we demonstrate that CpG-D NA sequence specifically triggers macrophages to produce IFN type I, interl eukin (IL)-12, IL-6 and tumour necrosis factor (TNF), but lacks the ability to directly costimulate T cells. Strikingly, poly-guanosine (poly-G) exten sions to CpG-containing oligonucleotides (ODN) abolished the macrophage sti mulatory potential yet generated T-cell costimulatory activities. In fact, independently of CpG-motifs, poly-G-ODN displayed the ability to costimulat e T cells. Costimulation was operative on CD8 T cells but not CD4 T cells. Poly-G-mediated costimulation resulted in IL-2-driven T-cell proliferation and induced cytolytic T cells. Overall the data imply that poly-G motifs co stimulate antigen reactive CD8 T cells, while CpG-DNA motifs fail to do so but may affect T-cell activation via APC derived cytokines such as IFN type I.