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Research Article Free access | 10.1172/JCI4160

GM-CSF transgene expression in the airway allows aerosolized ovalbumin to induce allergic sensitization in mice.

M R Stämpfli, R E Wiley, G S Neigh, B U Gajewska, X F Lei, D P Snider, Z Xing, and M Jordana

Department of Pathology and Molecular Medicine, Immunology and Infection Programme, and Centre for Gene Therapeutics, McMaster University, Hamilton, Ontario, Canada L8N 3Z5.

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Department of Pathology and Molecular Medicine, Immunology and Infection Programme, and Centre for Gene Therapeutics, McMaster University, Hamilton, Ontario, Canada L8N 3Z5.

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Department of Pathology and Molecular Medicine, Immunology and Infection Programme, and Centre for Gene Therapeutics, McMaster University, Hamilton, Ontario, Canada L8N 3Z5.

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Department of Pathology and Molecular Medicine, Immunology and Infection Programme, and Centre for Gene Therapeutics, McMaster University, Hamilton, Ontario, Canada L8N 3Z5.

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Department of Pathology and Molecular Medicine, Immunology and Infection Programme, and Centre for Gene Therapeutics, McMaster University, Hamilton, Ontario, Canada L8N 3Z5.

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Department of Pathology and Molecular Medicine, Immunology and Infection Programme, and Centre for Gene Therapeutics, McMaster University, Hamilton, Ontario, Canada L8N 3Z5.

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Department of Pathology and Molecular Medicine, Immunology and Infection Programme, and Centre for Gene Therapeutics, McMaster University, Hamilton, Ontario, Canada L8N 3Z5.

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Department of Pathology and Molecular Medicine, Immunology and Infection Programme, and Centre for Gene Therapeutics, McMaster University, Hamilton, Ontario, Canada L8N 3Z5.

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Published November 1, 1998 - More info

Published in Volume 102, Issue 9 on November 1, 1998
J Clin Invest. 1998;102(9):1704–1714. https://doi.org/10.1172/JCI4160.
© 1998 The American Society for Clinical Investigation
Published November 1, 1998 - Version history
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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.

Version history
  • Version 1 (November 1, 1998): No description
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