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-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.
Stämpfli
M R
MR
Department of Pathology and Molecular Medicine, Immunology and Infection Programme, and Centre for Gene Therapeutics, McMaster University, Hamilton, Ontario, Canada L8N 3Z5.
Wiley
R E
RE
Neigh
G S
GS
Gajewska
B U
BU
Lei
X F
XF
Snider
D P
DP
Xing
Z
Z
Jordana
M
M
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
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