title: A novel adjuvant-allergen complex, CBP-rFel d 1, induces up-regulation of CD86 expression and enhances cytokine release by human dendritic cells in vitro.
abstract: Allergen-specific immunotherapy is commonly performed with allergen extracts adsorbed to aluminium hydroxide (alum). The undesirable effects associated with the use of alum, including granuloma formation at the site of injection and stimulation of T helper 2 (Th2) cytokine production, has generated interest in alternative allergen carriers, one being carbohydrate-based particles (CBPs). Here, we have investigated the in vitro effects of the recombinant major cat allergen Fel d 1 (rFel d 1) coupled to CBPs (CBP-rFel d 1) on human monocyte-derived dendritic cells (MDDCs) obtained from healthy blood donors. A majority of the CD1a(+) MDDCs internalized fluorescein isothiocyanate-labelled CBP-rFel d 1, as demonstrated by flow cytometry and confocal laser-scanning microscopy. Furthermore, an up-regulation of the expression of the costimulatory molecule, CD86, on the MDDCs was induced by CBP-rFel d 1, but not by rFel d 1 or CBPs alone. Finally, three- and fourfold increases in the release of interleukin-8 and tumour necrosis factor-alpha, respectively, were observed when MDDCs were cultured in the presence of CBP-rFel d 1. Altogether, our results indicate that the use of CBPs as an allergen carrier and adjuvant is a promising candidate for the improvement of allergen-specific immunotherapy.
authors.affiliation: Department of Medicine, Clinical Immunology and Allergy Unit, Karolinska Institutet and University Hospital, Stockholm, Sweden.
authors.forename: Theresa N
authors.initials: TN
authors.lastname: Andersson
authors.forename: Gunilla J
authors.initials: GJ
authors.lastname: Ekman
authors.forename: Hans
authors.initials: H
authors.lastname: Grönlund
authors.forename: Eva
authors.initials: E
authors.lastname: Buentke
authors.forename: Tove L J
authors.initials: TL
authors.lastname: Eriksson
authors.forename: Annika
authors.initials: A
authors.lastname: Scheynius
authors.forename: Marianne
authors.initials: M
authors.lastname: Van Hage-Hamsten
authors.forename: Guro
authors.initials: G
authors.lastname: Gafvelin
mesh_terms: D000276:Adjuvants, Immunologic / Q000502:physiology; D000485:Allergens / Q000276:immunology*; D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D000954:Antigens, Surface / Q000276:immunology; D051940:B7-2 Antigen; D002415:Cats; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D005434:Flow Cytometry / Q000379:methods; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D016209:Interleukin-8 / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology*; D018613:Microscopy, Confocal / Q000379:methods; D011994:Recombinant Proteins / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000485:Allergens; D015703:Antigens, CD; D000954:Antigens, Surface; D051940:B7-2 Antigen; C497964:CD86 protein, human; D016207:Cytokines; D006023:Glycoproteins; D016209:Interleukin-8; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; C059296:Fel d 1 protein, Felis domesticus