title: GM-CSF transgene expression in the airway allows aerosolized ovalbumin to induce allergic sensitization in mice.
abstract: The purpose of this study was to explore whether repeated exposure to aerosolized ovalbumin (OVA) in the context of local expression of GM-CSF 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 were exposed daily to an OVA aerosol. Mice exposed to OVA alone did not show any evidence of airway inflammation. Mice receiving both Ad/GM-CSF and aerosolized OVA exhibited marked airway inflammation characterized by eosinophilia and goblet cell hyperplasia. Migration of eosinophils into the airway was preceded by a rise in IL-5 and IL-4. Both IL-5 and class II MHC were critically required to generate airway eosinophilia. After resolution, airway eosinophilia was reconstituted after a single OVA exposure. Flow cytometric analysis of dispersed lung cells revealed an increase in macrophages and dendritic cells expressing B7.1 and B7.2, and expansion of activated (CD69-expressing) CD4 and CD8 T cells in mice exposed to OVA and Ad/GM-CSF. Our data indicate that expression of GM-CSF in the airway compartment increases local antigen presentation capacity, and concomitantly facilitates the development of an antigen-specific, eosinophilic inflammatory response to an otherwise innocuous antigen.
authors.affiliation: Department of Pathology and Molecular Medicine, Immunology and Infection Programme, and Centre for Gene Therapeutics, McMaster University, Hamilton, Ontario, Canada L8N 3Z5.
authors.forename: M R
authors.initials: MR
authors.lastname: Stämpfli
authors.forename: R E
authors.initials: RE
authors.lastname: Wiley
authors.forename: G S
authors.initials: GS
authors.lastname: Neigh
authors.forename: B U
authors.initials: BU
authors.lastname: Gajewska
authors.forename: X F
authors.initials: XF
authors.lastname: Lei
authors.forename: D P
authors.initials: DP
authors.lastname: Snider
authors.forename: Z
authors.initials: Z
authors.lastname: Xing
authors.forename: M
authors.initials: M
authors.lastname: Jordana
mesh_terms: D000260:Adenoviruses, Human; D000336:Aerosols; D000485:Allergens / Q000276:immunology; D000818:Animals; D000941:Antigens / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D004804:Eosinophils / Q000276:immunology; D005260:Female; D015870:Gene Expression; D005822:Genetic Vectors; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D018928:Immunity, Mucosal; D015847:Interleukin-4 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D008168:Lung / Q000276:immunology* / Q000473:pathology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D013997:Time Factors; D019076:Transgenes
chemical_list: D000336:Aerosols; D000485:Allergens; D000941:Antigens; D000949:Histocompatibility Antigens Class II; D015848:Interleukin-5; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D010047:Ovalbumin