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.
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.
Andersson
Theresa N
TN
Department of Medicine, Clinical Immunology and Allergy Unit, Karolinska Institutet and University Hospital, Stockholm, Sweden.
Ekman
Gunilla J
GJ
Grönlund
Hans
H
Buentke
Eva
E
Eriksson
Tove L J
TL
Scheynius
Annika
A
Van Hage-Hamsten
Marianne
M
Gafvelin
Guro
G
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
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