Immunomodulatory nanoparticles as adjuvants and allergen-delivery system to human dendritic cells: Implications for specific immunotherapy

Abstract

Novel adjuvants and antigen-delivery systems with immunomodulatory properties that shift the allergenic Th2 response towards a Th1 or regulatory T cell response are desired for allergen-specific immunotherapy. This study demonstrates that 200-nm sized biodegradable poly(γ-glutamic acid) (γ-PGA) nanoparticles (NPs) are activators of human monocyte-derived dendritic cells (MoDCs). γ-PGA NPs are efficiently internalized by immature MoDCs and strongly stimulate production of chemokines and inflammatory cytokines as well as up-regulation of co-stimulatory molecules and immunomodulatory mediators involved in efficient T cell priming. Furthermore, MoDCs from allergic subjects stimulated in vitro with a mixture of γ-PGA NPs and extract of grass pollen allergen Phleum pratense ( Phl p) augment allergen-specific IL-10 production and proliferation of autologous CD4 + memory T cells. Thus, γ-PGA NPs are promising as sophisticated adjuvants and allergen-delivery systems in allergen-specific immunotherapy.