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

European Journal of Immunology
Kouji KobiyamaKen J Ishii

Abstract

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 β-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 CD8α(+) DCs, as well as the secreted cytokines, IFN-α and IL-12, we found that K3-SPG strongly activates mouse plasmacytoid DCs to secrete IFN-α and CD8α(+) 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-γ 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(+) ...Continue Reading

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Citations

Sep 24, 2019·Scandinavian Journal of Immunology·Vaclav VetvickaPetr Sima
May 1, 2020·Frontiers in Chemistry·Shuyao Lang, Xuefei Huang
Dec 5, 2020·Journal of Autoimmunity·Francesca MottaCarlo Selmi
Jun 9, 2021·Expert Review of Vaccines·Xinyuan ZhangQinjian Zhao
Jul 30, 2021·International Journal of Nanomedicine·Huajun ZhaoJian Zhang
Feb 11, 2021·Recent Patents on Anti-cancer Drug Discovery·Yu YanXiaoyu Li

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