Immunomodulatory nanoparticles as adjuvants and allergen-delivery system to human dendritic cells: Implications for specific immunotherapy.
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(gamma-glutamic acid) (gamma-PGA) nanoparticles (NPs) are activators of human monocyte-derived dendritic cells (MoDCs). Gamma-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 gamma-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, gamma-PGA NPs are promising as sophisticated adjuvants and allergen-delivery systems in allergen-specific immunotherapy.
Broos
Sissela
S
Department of Immunotechnology, Lund University, Lund, Sweden.
Lundberg
Kristina
K
Akagi
Takami
T
Kadowaki
Koji
K
Akashi
Mitsuru
M
Greiff
Lennart
L
Borrebaeck
Carl A K
CA
Lindstedt
Malin
M
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000485:Allergens / Q000276:immunology*; D017951:Antigen Presentation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D016503:Drug Delivery Systems; D020869:Gene Expression Profiling; D006801:Humans; D007156:Immunologic Memory; D007167:Immunotherapy; D016753:Interleukin-10 / Q000276:immunology; D053758:Nanoparticles; D020411:Oligonucleotide Array Sequence Analysis; D006109:Poaceae / Q000276:immunology; D011058:Pollen / Q000276:immunology; D011099:Polyglutamic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D051195:Toll-Like Receptor 2 / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000276:immunology
D000276:Adjuvants, Immunologic; D000485:Allergens; C508609:IL10 protein, human; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; C511775:poly(gamma-glutamic acid); D016753:Interleukin-10; D011099:Polyglutamic Acid