A Novel Adjuvant Allergen Complex, CBP‐Fel d 1, Induces Upregulation of CD86 and Cytokine Release in Human Dendritic Cells

Neimert‐Andersson, T.; Ekman, G. J.; Grönlund, H.; Buentke, E.; Scheynius, A.; Van Hage‐Hamsten, M.; Gafvelin, G.

Allergen‐specific immunotherapy (SIT) is commonly conducted with allergen extracts adsorbed to aluminium hydroxide (alum). Drawbacks linked to the use of alum, such as the formation of granuloma at the site of injection, have led to suggestions of novel allergen carriers. An alternative carrier is 2 μm carbohydrate‐based particles (CBPs). In mouse, allergen‐coupled CBPs have been demonstrated to skew the allergen‐specific immune response towards a Th1‐like activity (Grönlund et al. Immunology, 2002). We here coupled the recombinant major cat allergen Fel d 1 to CBPs (CBP‐Fel d 1) by cyanogen‐bromide activation, resulting in covalent binding. The effect of CBP‐Fel d 1 on monocyte‐derived dendritic cells (MDDCs) from healthy human blood donors was studied. We found that the majority of the CD1a(+) MDDCs were capable of taking up FITC‐labelled CBP‐Fel d 1, as demonstrated by flow cytometry and confocal laser scanning microscopy. Furthermore, incubation with CBP‐Fel d 1 resulted in an upregulation of the costimulatory molecule CD86 on the MDDCs, which was not observed with Fel d 1 or CBPs alone. Finally, CBP‐Fel d 1 induced a fivefold increase in the release of the pro‐inflammatory cytokine tumour necrosis factor (TNF)‐α and a fourfold increase in the release of the chemokine interleukin‐8 from MDDCs. Taken together, the effects CBPs possess make them interesting as novel allergen carriers for SIT.