title: Species-dependent role of type I IFNs and IL-12 in the CTL response induced by humanized CpG complexed with β-glucan.
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(+) T-cell responses despite the differential role of IL-12 between human and mice.
authors.affiliation: Laboratory of Adjuvant Innovation, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki, Osaka, Japan.|Laboratory of Vaccine Science, World Premier International Research Center, Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan.
authors.forename: Kouji
authors.initials: K
authors.lastname: Kobiyama
authors.affiliation: Laboratory of Vaccine Science, World Premier International Research Center, Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan.
authors.forename: Burcu
authors.initials: B
authors.lastname: Temizoz
authors.affiliation: Laboratory of Adjuvant Innovation, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki, Osaka, Japan.|Laboratory of Vaccine Science, World Premier International Research Center, Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kanuma
authors.affiliation: Laboratory of Adjuvant Innovation, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki, Osaka, Japan.|Department of Pediatrics, Yokohama City University, Kanazawaku, Yokohama, Kanagawa, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Ozasa
authors.affiliation: Laboratory of Adjuvant Innovation, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki, Osaka, Japan.|Laboratory of Vaccine Science, World Premier International Research Center, Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Momota
authors.affiliation: Laboratory of Adjuvant Innovation, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki, Osaka, Japan.|Laboratory of Vaccine Science, World Premier International Research Center, Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Yamamoto
authors.affiliation: Laboratory of Adjuvant Innovation, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki, Osaka, Japan.|Laboratory of Vaccine Science, World Premier International Research Center, Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan.
authors.forename: Taiki
authors.initials: T
authors.lastname: Aoshi
authors.affiliation: Laboratory of Vaccine Science, World Premier International Research Center, Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan.
authors.forename: Etsushi
authors.initials: E
authors.lastname: Kuroda
authors.affiliation: Laboratory of Adjuvant Innovation, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki, Osaka, Japan.|Laboratory of Vaccine Science, World Premier International Research Center, Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan.
authors.forename: Ken J
authors.initials: KJ
authors.lastname: Ishii
mesh_terms: D000276:Adjuvants, Immunologic; D000328:Adult; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D016898:Interferon-alpha / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology; D018664:Interleukin-12 / Q000172:deficiency / Q000276:immunology* / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology; D018417:Th1 Cells / Q000276:immunology; D051217:Toll-Like Receptor 9 / Q000819:agonists; D047071:beta-Glucans / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D016898:Interferon-alpha; D009838:Oligodeoxyribonucleotides; D051217:Toll-Like Receptor 9; D047071:beta-Glucans; D018664:Interleukin-12; D007371:Interferon-gamma
keywords: Adjuvant; CD8+ T cells; CpG ODN ⋅ IL-12; Nanoparticle; Type I IFN