CpG-oligodeoxynucleotides enhance T-cell receptor-triggered interferon-gamma production and up-regulation of CD69 via induction of antigen-presentingcell-derived interferon type I and interleukin-12

Bacterial cytidine-phosphate-guanosine (CpG-DNA) activates antigen-presenti ng cells (APC) and drives T helper 1 (Th1)-polarized immune responses in th e mouse. Claims have been made that CpG-DNA costimulates murine T cells. We examined the direct and indirect effects of CpG-oligodeoxynucleotides (CpG -ODN) on human T-cell activation. CpG-ODN failed to costimulate purified hu man T cells activated with alpha-CD3 or alpha-T-cell receptor (TCR)alpha be ta antibodies. In contrast, CpG-ODN sequence-specifically caused increased expression of CD69 on CD4 and CD8 T cells when peripheral blood mononuclear cells (PBMC) were stimulated via alpha-CD3. CpG-ODN and alpha-CD3 stimulat ion synergized to induce interferon-gamma (IFN-gamma) in T cells and natura l killer (NK) cells, as shown by intracellular fluorescence-activated cell sorter (FACS) staining. These effects of CpG-ODN on human T cells were caus ed by the release of IFN type I (IFN-I) and interleukin-12 (IL-12) from PBM C. Enhancement of CD69 expression on alpha-CD3-triggered T cells could be r eproduced in a coculture transwell system of purified T cells and PBMC, was inhibited by neutralizing antibodies to IFN-I and could be mimicked by add ing exogenous IFN-I. Furthermore, neutralization of either IFN-I or IL-12 d iminished, and in combination abolished, IFN-gamma production. These findin gs show that CpG-ODN potentiate TCR-triggered activation of human T cells i n an APC-dependent manner.