title: Protein-bound polysaccharide activates dendritic cells and enhances OVA-specific T cell response as vaccine adjuvant.
abstract: Protein-bound polysaccharide-K (PSK) is a hot water extract from Trametes versicolor mushroom. It has been used traditionally in Asian countries for its immune stimulating and anti-cancer effects. We have recently found that PSK can activate Toll-like receptor 2 (TLR2). TLR2 is highly expressed on dendritic cells (DC), so the current study was undertaken to evaluate the effect of PSK on DC activation and the potential of using PSK as a vaccine adjuvant. In vitro experiments using mouse bone marrow-derived DC (BMDC) demonstrated that PSK induces DC maturation as shown by dose-dependent increase in the expression of CD80, CD86, MHCII, and CD40. PSK also induces the production of multiple inflammatory cytokines by DC, including IL-12, TNF-α, and IL-6, at both mRNA and protein levels. In vivo experiments using PSK as an adjuvant to OVAp323-339 vaccine showed that PSK as adjuvant leads to enlarged draining lymph nodes with higher number of activated DC. PSK also stimulates proliferation of OVA-specific T cells, and induces T cells that produce multiple cytokines, IFN-γ, IL-2, and TNF-α. Altogether, these results demonstrate the ability of PSK to activate DC in vitro and in vivo and the potential of using PSK as a novel vaccine adjuvant.
authors.affiliation: Bastyr University, Kenmore, WA, United States. Electronic address: aengel@bastyr.edu.
authors.forename: Abbi L
authors.initials: AL
authors.lastname: Engel
authors.forename: Guan-Cheng
authors.initials: GC
authors.lastname: Sun
authors.forename: Ekram
authors.initials: E
authors.lastname: Gad
authors.forename: Lauren R
authors.initials: LR
authors.lastname: Rastetter
authors.forename: Katie
authors.initials: K
authors.lastname: Strobe
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.forename: Yushe
authors.initials: Y
authors.lastname: Dang
authors.forename: Mary L
authors.initials: ML
authors.lastname: Disis
authors.forename: Hailing
authors.initials: H
authors.lastname: Lu
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D018836:Inflammation Mediators / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D011509:Proteoglycans / Q000008:administration & dosage*; D037182:T-Cell Antigen Receptor Specificity; D013601:T-Lymphocytes / Q000276:immunology*; D055454:Trametes / Q000276:immunology; D015854:Up-Regulation / Q000187:drug effects; D022223:Vaccines, Subunit
chemical_list: D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D016207:Cytokines; D018836:Inflammation Mediators; C111390:OVA 323-339; D010446:Peptide Fragments; D011509:Proteoglycans; D022223:Vaccines, Subunit; C010770:polysaccharide-K; D010047:Ovalbumin
keywords: BMDC; CAM; CFSE; CTL; DC; Dendritic cells; FBS; GM-CSF; IFN-γ; IL; OVA; OVA peptide; PBS; PRR; PSK; TLR; TNF-α; Toll-like receptor; Vaccine; bone marrow-derived DC; carboxyfluorescein diacetate succinimidyl ester; complementary and alternative medicine; cytotoxic T lymphocyte; dendritic cells; fetal bovine serum; granulocytes macrophages-colony stimulating factor; interferon gamma; interleukin; mAb; monoclonal antibody; ovalbumin; pattern recognition receptors; phosphate buffered saline; protein-bound polysaccharide-K (Kureha); tumor necrosis factor alpha