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Sensitization to inhaled antigen by intratracheal instillation of dendritic cells
Authors:Lambrecht,Peleman,Bullock,&   Pauwels
Affiliation:Respiratory Diseases; Pathology, University Hospital Ghent, Belgium. lambrech@longz.fgg.eur.nl
Abstract:BACKGROUND: Airway dendritic cells (DCs) capture and present inhaled antigen. It is not known whether antigen presentation by DCs in the airways is sufficient to induce sensitization to inhaled antigen in vivo. METHODS: Rats were immunized by intratracheal instillation of ovalbumin (OVA) -pulsed bone marrow-derived DCs or macrophages and exposed 10 days later to a 30-min aerosol of OVA on 3 consecutive days. Total and differential cell counts and flow cytometry on bronchoalveolar lavage (BAL) fluid, airway histology and serum OVA-immunoglobulin (Ig) E levels were analysed 24 h after the last exposure. RESULTS: As few as 2 x 104 OVA-DC induced sensitization to inhaled OVA. The secondary response to OVA-aerosol consisted of an antigen-specific increase in the number of bronchoalveolar mononuclear cells, activated CD4-positive alphabeta-TCR T lymphocytes, neutrophils and few eosinophils. Peribronchial and perivascular mononuclear cell infiltrates were seen on histological analysis. There was no production of systemic OVA-IgE. Bone marrow-derived macrophages did not induce sensitization. CONCLUSION: Delivering antigen to the respiratory tract via professional antigen-presenting DCs sensitizes for a secondary response to inhaled antigen leading to airway inflammation. This model will prove very useful for studying the early events of sensitization to inhaled antigen using the respiratory route.
Keywords:airway inflammation    asthma    Brown Norway rat    costimulation    dendritic cell    sensitization
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