Dendritic cells are required for the development of chronic eosinophilic airway inflammation in response to inhaled antigen in sensitized mice.
Asthma is characterized by chronic eosinophilic inflammation of the airways, and allergen-specific Th2 lymphocytes are thought to play a major role in the development and maintenance of this type of inflammation in allergic asthma. It is generally accepted that airway dendritic cells (DC) are essential for stimulating naive T cells in a primary immune response to inhaled Ag and for the development of allergic sensitization. We have examined the role of airway DC in stimulating memory T cells in a secondary response to inhaled Ag and the subsequent development of chronic airway inflammation. In our mouse model of asthma, OVA aerosol challenge in OVA-sensitized mice leads to CD4-dependent peribronchial and perivascular eosinophilic inflammation, lung Th2 cytokine production, and systemic IgE production. We have used conditional depletion of airway DC by treatment of thymidine kinase-transgenic mice with the antiviral drug ganciclovir to deplete DC during the secondary exposure to OVA. In sensitized thymidine kinase-transgenic mice, a significant decrease in the number of bronchoalveolar CD4 and CD8 T lymphocytes and B lymphocytes was seen after ganciclovir treatment. In addition, Th2 cytokine-associated eosinophilic airway inflammation was almost completely suppressed. These studies demonstrate for the first time that the DC is essential for presenting inhaled Ag to previously primed Th2 cells in the lung, leading to chronic eosinophilic airway inflammation. Altering the function of airway DC may therefore be an important target for new anti-asthma therapy.
Lambrecht
B N
BN
Department of Respiratory Diseases, University Hospital, Ghent, Belgium. bart.lambrecht@rug.ac.be
Salomon
B
B
Klatzmann
D
D
Pauwels
R A
RA
D000280:Administration, Inhalation; D000818:Animals; D000941:Antigens / Q000008:administration & dosage; D001249:Asthma / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D001402:B-Lymphocytes / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D003713:Dendritic Cells / Q000473:pathology / Q000502:physiology*; D004802:Eosinophilia / Q000209:etiology / Q000276:immunology / Q000473:pathology; D004804:Eosinophils / Q000473:pathology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology
D000941:Antigens; D010047:Ovalbumin