Species-dependent role of type I IFNs and IL-12 in the CTL response induced by humanized CpG complexed with [beta]-glucan

CpG oligodeoxynucleotide (ODN) is one of promising nucleic acid-based adjuvants. We recently improved its ability to enhance CD8+ T-cell responses to coadministered protein antigen without conjugation or emulsion, by forming a nanoparticulate complex between CpG ODN (K3) and mushroom-derived [beta]-glucan schizophyllan (SPG), namely K3-SPG. Here, we sought to elucidate the cellular immunological mechanisms by which K3-SPG induce such potent CD8+ T-cell responses to coadministered antigen. By focusing on two DC subsets, plasmacytoid DCs and CD8[alpha]+ DCs, as well as the secreted cytokines, IFN-[alpha] and IL-12, we found that K3-SPG strongly activates mouse plasmacytoid DCs to secrete IFN-[alpha] and CD8[alpha]+ DCs to secrete IL-12, respectively. Although a single cytokine deficiency had no impact on adjuvant effects, the lack of both type I IFN and IL-12 in mice resulted in a significant reduction of Th1 type immune responses and CD8+ T-cell responses elicited by protein vaccine model. By sharp contrast, type I IFN, but not IL-12, was required for the production of IFN-[gamma] by human PBMCs as well as antigen-specific CD8+ T-cell proliferation. Taken together, K3-SPG may overcome the species barrier for CpG ODN to enhance antigen-specific CD8+ T-cell responses despite the differential role of IL-12 between human and mice.