GM-CSF TRANSGENE EXPRESSION IN THE AIRWAY ALLOWS AEROSOLIZED OVALBUMIN TO INDUCE ALLERGIC SENSITIZATION IN MICE

The purpose of this study was to explore whether repeated exposure to aerosolized ovalbumin (OVA) in the context of local expression of GM-C SF can initiate a Th2-driven, eosinophilic inflammation in the airways . On day -1, Balb/c mice were infected intranasally with an adenovirus construct expressing GM-CSF (Ad/GM-CSF), From day 0 to day 9 mice wer e exposed daily to an OVA aerosol. Mice exposed to OVA alone did not s how any evidence of airway inflammation. Mice receiving both Ad/GM-CSF and aerosolized OVA exhibited marked airway inflammation characterize d by eosinophilia and goblet cell hyperplasia. Migration of eosinophil s into the airway was preceded by a rise in IL-5 and IL-4. Both IL-5 a nd class II MHC were critically required to generate airway eosinophil ia. After resolution, airway eosinophilia was reconstituted after a si ngle OVA exposure. Flow cytometric analysis of dispersed lung cells re vealed an increase in macrophages and dendritic cells expressing B7.1 and B7.2, and expansion of activated (CD69-expressing) CD4 and CD8 T c ells in mice exposed to OVA and Ad/GM-CSF, Our data indicate that expr ession of GMCSF in the airway compartment increases local antigen pres entation capacity, and concomitantly facilitates the development of an antigen-specifics, eosinophilic inflammatory response to an otherwise innocuous antigen.