Ovalbumin aerosols induce airway hyperreactivity in naïve DO11.10 T cell receptor transgenic mice without pulmonary eosinophilia or OVA-specific antibody.
The pathobiology of allergic asthma is being studied using murine models, most of which use systemic priming followed by pulmonary challenges with the immunizing antigen. In general, mice develop eosinophilic pulmonary inflammation, increased antigen-specific immunoglobulins, and airway hyperreactivity (AHR), all of which are dependent on antigen-specific T cell activation. To establish a model of allergic asthma, which did not require systemic priming, we exposed DO11.10 T cell receptor transgenic mice, which have an expanded repertoire of ovalbumin (OVA), peptide-specific T cells, to limited aerosols of OVA protein. DO11.10 +/- mice developed AHR in the absence of increases in total serum IgE, OVA-specific IgG, or eosinophilia. The AHR was accompanied by pulmonary recruitment of antigen-specific T cells with decreased expression of CD62L and CD45RB and increased expression of CD69, a phenotype indicative of T cell activation. Our results support recent hypotheses that T cells mediate AHR directly.
Wilder
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JA
University of New Mexico, Department of Pathology, Albuquerque, New Mexico 87131, USA. jwilder@salud.unm.edu
Collie
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Bice
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Tesfaigzi
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Lyons
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Lipscomb
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D000281:Administration, Intranasal; D000336:Aerosols; D000403:Airway Resistance; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000139:chemically induced*; D016207:Cytokines / Q000032:analysis; D004802:Eosinophilia; D005260:Female; D007114:Immunization; D007115:Immunization Schedule; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D016130:Immunophenotyping; D008168:Lung / Q000473:pathology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D023421:Models, Animal; D010047:Ovalbumin / Q000008:administration & dosage / Q000633:toxicity*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D013047:Specific Pathogen-Free Organisms
D000336:Aerosols; D016207:Cytokines; D007074:Immunoglobulin G; D016693:Receptors, Antigen, T-Cell, alpha-beta; D007073:Immunoglobulin E; D010047:Ovalbumin