title: Chronic exposure to innocuous antigen in sensitized mice leads to suppressed airway eosinophilia that is reversed by granulocyte macrophage colony-stimulating factor.
abstract: In this study we investigated the impact of chronic allergen exposure on airway inflammation and humoral responses in sensitized mice. We observed marked eosinophilia in the bronchoalveolar lavage, lung tissue, and peripheral blood after 2 wk of exposure. In contrast, eosinophilia was markedly reduced by 3 wk and completely resolved by 4 wk of exposure, despite the continued presence of Ag. Decreases in airway eosinophilia were associated with a robust humoral response. We observed that levels of OVA-specific IgE, IgG1, and IgG2a increased during the course of exposure. To assess whether continuous exposure to Ag impacts the ability of the lung to respond to subsequent Ag challenge, mice were exposed to either 2 or 4 wk of OVA in the context of GM-CSF. All groups were then rested for 28 days and exposed to OVA on three consecutive days. We observed a significant decrease in airway eosinophilia and IL-5 expression in the bronchoalveolar lavage and serum in mice initially exposed to 4 wk of OVA, compared with animals exposed to 2 wk only. However, in both groups expression of B7.2 on dendritic cells as well as CD25, CD69, and T1/ST2 on CD4(+) T cells was enhanced, suggesting immune activation. Delivery of rGM-CSF fully restored airway eosinophilia. This study shows that exposure to innocuous Ag alone does not lead to persistent eosinophilic airway inflammation, but rather to abrogated eosinophilia. This suppression can be reversed by GM-CSF.
authors.affiliation: Department of Pathology and Molecular Medicine, Division of Respiratory Diseases and Allergy and Center for Gene Therapeutics, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Filip K
authors.initials: FK
authors.lastname: Swirski
authors.forename: Dusan
authors.initials: D
authors.lastname: Sajic
authors.forename: Clinton S
authors.initials: CS
authors.lastname: Robbins
authors.forename: Beata U
authors.initials: BU
authors.lastname: Gajewska
authors.forename: Manel
authors.initials: M
authors.lastname: Jordana
authors.forename: Martin R
authors.initials: MR
authors.lastname: Stämpfli
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D000941:Antigens / Q000008:administration & dosage* / Q000097:blood / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D004334:Drug Administration Schedule; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage*; D007108:Immune Tolerance; D007114:Immunization / Q000379:methods; D007117:Immunization, Secondary; D007073:Immunoglobulin E / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D007156:Immunologic Memory; D016130:Immunophenotyping; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000008:administration & dosage* / Q000097:blood / Q000276:immunology; D011657:Pulmonary Eosinophilia / Q000097:blood / Q000276:immunology* / Q000517:prevention & control*; D011994:Recombinant Proteins; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism
chemical_list: D000941:Antigens; D007074:Immunoglobulin G; D011994:Recombinant Proteins; D007073:Immunoglobulin E; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D010047:Ovalbumin