Prolonged ovalbumin exposure attenuates airway hyperresponsiveness and T cell function in mice.
BACKGROUND
Continuous exposure of sensitized mice to an innocuous antigen, such as OVA, does not lead to chronic airway eosinophilia, but induces antigen unresponsiveness and resolution of the inflammatory response. In this study we explored mechanisms underlying attenuation of the airway inflammatory response, assessed whether the phenomenon is strain-specific, and determined its consequences to airway physiology.


METHODS
Mice were sensitized and exposed to OVA for two and four weeks. Analysis involved BAL, flow cytometry, adoptive transfer of OVA specific CD4 T cells, ex vivo cytokine expression and response to methacholine challenge.


RESULTS
Chronic exposure to antigen resulted in decreased eosinophilia in 5 different mouse strains. Likewise, numbers of lung CD4 T cells expressing activation and Th2 markers sharply declined following continuous OVA exposure. Transfer studies using OVA TcR transgenic cells revealed that the contraction of lung T cells included antigen-specific cells. Systemically, we observed a loss of Th2 memory effector function. Finally, we observed significantly attenuated airway hyper-responsiveness (AHR) in chronically exposed animals.


CONCLUSIONS
Attenuation of airway eosinophilia in response to chronic OVA exposure is independent of genetic background. Airway eosinophilia, but not systemic responses, correlates with and is predictive for airway hyperresponsiveness. Our study contributes to the understanding of immune regulatory processes controlling antigen-driven airway inflammatory responses.
Swirski
Filip K
FK
Department of Pathology and Molecular Medicine, Centre for Gene Therapeutics, Hamilton, Canada. fswirski@rics.bwh.harvard.edu
D'Sa
Abigail
A
Kianpour
Sussan
S
Inman
Mark D
MD
Stämpfli
Martin R
MR
D019264:Adoptive Transfer; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000276:immunology*; D001985:Bronchial Provocation Tests; D018893:Bronchoalveolar Lavage; D016085:Bronchoconstrictor Agents / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D004802:Eosinophilia / Q000139:chemically induced / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D007156:Immunologic Memory / Q000187:drug effects; D016210:Methacholine Chloride / Q000494:pharmacology; D051379:Mice; D010047:Ovalbumin / Q000276:immunology* / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D013997:Time Factors
D016085:Bronchoconstrictor Agents; D016207:Cytokines; D016210:Methacholine Chloride; D010047:Ovalbumin