CpG‐oligodeoxynucleotides enhance T‐cell receptor‐triggered interferon‐γ production and up‐regulation of CD69 via induction of antigen‐presenting cell‐derived interferon type I and interleukin‐12

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Abstract
Bacterial cytidine–phosphate–guanosine (CpG-DNA) activates antigen-presenting cells (APC) and drives T helper 1 (Th1)-polarized immune responses in the 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 human T cells activated with α-CD3 or α-T-cell receptor (TCR)αβ 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 α-CD3. CpG-ODN and α-CD3 stimulation synergized to induce interferon-γ (IFN-γ) in T cells and natural killer (NK) cells, as shown by intracellular fluorescence-activated cell sorter (FACS) staining. These effects of CpG-ODN on human T cells were caused by the release of IFN type I (IFN-I) and interleukin-12 (IL-12) from PBMC. Enhancement of CD69 expression on α-CD3-triggered T cells could be reproduced in a coculture transwell system of purified T cells and PBMC, was inhibited by neutralizing antibodies to IFN-I and could be mimicked by adding exogenous IFN-I. Furthermore, neutralization of either IFN-I or IL-12 diminished, and in combination abolished, IFN-γ production. These findings show that CpG-ODN potentiate TCR-triggered activation of human T cells in an APC-dependent manner.