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.

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.