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*
Department of Respiratory Diseases, University Hospital, B-9000 Ghent, Belgium; and
Laboratoire de Biologie et Thérapeutique de Pathologies Immunitaires, Centre National de la Recherche Scientifique ERS 107, Hôpital de la Pitié-Salpêtrière, 75651 Paris Cedex 13, France
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.
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Q. Ye, P. W. Finn, R. Sweeney, E. K. Bikoff, and R. J. Riese MHC Class II-Associated Invariant Chain Isoforms Regulate Pulmonary Immune Responses J. Immunol., February 1, 2003; 170(3): 1473 - 1480. [Abstract] [Full Text] [PDF]
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A.-S. Charbonnier, H. Hammad, P. Gosset, G. A. Stewart, S. Alkan, A.-B. Tonnel, and J. Pestel Der p 1-pulsed myeloid and plasmacytoid dendritic cells from house dust mite-sensitized allergic patients dysregulate the T cell response J. Leukoc. Biol., January 1, 2003; 73(1): 91 - 99. [Abstract] [Full Text] [PDF]
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N. Omata, M. Yasutomi, A. Yamada, H. Iwasaki, M. Mayumi, and Y. Ohshima Monocyte Chemoattractant Protein-1 Selectively Inhibits the Acquisition of CD40 Ligand-Dependent IL-12-Producing Capacity of Monocyte-Derived Dendritic Cells and Modulates Th1 Immune Response J. Immunol., November 1, 2002; 169(9): 4861 - 4866. [Abstract] [Full Text] [PDF]
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C. A. Byersdorfer and D. D. Chaplin Visualization of Early APC/T Cell Interactions in the Mouse Lung Following Intranasal Challenge J. Immunol., December 15, 2001; 167(12): 6756 - 6764. [Abstract] [Full Text] [PDF]
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 F L Jahnsen, E D Moloney, T Hogan, J W Upham, C M Burke, and P G Holt Rapid dendritic cell recruitment to the bronchial mucosa of patients with atopic asthma in response to local allergen challenge Thorax, November 1, 2001; 56(11): 823 - 826. [Abstract] [Full Text] [PDF]
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K. Y. Vermaelen, I. Carro-Muino, B. N. Lambrecht, and R. A. Pauwels Specific Migratory Dendritic Cells Rapidly Transport Antigen from the Airways to the Thoracic Lymph Nodes J. Exp. Med., January 1, 2001; 193(1): 51 - 60. [Abstract] [Full Text] [PDF]
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P. G. HOLT Antigen Presentation in the Lung Am. J. Respir. Crit. Care Med., October 1, 2000; 162(4): S151 - 156. [Abstract] [Full Text] [PDF]
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J. C. KIPS, K. G. TOURNOY, and R. A. PAUWELS Gene Knockout Models of Asthma Am. J. Respir. Crit. Care Med., September 1, 2000; 162(3): S66 - 70. [Full Text] [PDF]
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J. Reibman, A. T. Talbot, Y. Hsu, G. Ou, J. Jover, D. Nilsen, and M. H. Pillinger Regulation of Expression of Granulocyte-Macrophage Colony-Stimulating Factor in Human Bronchial Epithelial Cells: Roles of Protein Kinase C and Mitogen-Activated Protein Kinases J. Immunol., August 1, 2000; 165(3): 1618 - 1625. [Abstract] [Full Text] [PDF]
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K. HAMADA, C.-A. GOLDSMITH, A. GOLDMAN, and L. KOBZIK Resistance of Very Young Mice to Inhaled Allergen Sensitization Is Overcome by Coexposure to an Air-Pollutant Aerosol Am. J. Respir. Crit. Care Med., April 1, 2000; 161(4): 1285 - 1293. [Abstract] [Full Text]
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B. N. Lambrecht, R. A. Pauwels, and B. Fazekas de St. Groth Induction of Rapid T Cell Activation, Division, and Recirculation by Intratracheal Injection of Dendritic Cells in a TCR Transgenic Model J. Immunol., March 15, 2000; 164(6): 2937 - 2946. [Abstract] [Full Text] [PDF]
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D. A. Mark, C. E. Donovan, G. T. De Sanctis, H. Z. He, M. Cernadas, L. Kobzik, D. L. Perkins, A. Sharpe, and P. W. Finn B7-1 (CD80) and B7-2 (CD86) Have Complementary Roles in Mediating Allergic Pulmonary Inflammation and Airway Hyperresponsiveness Am. J. Respir. Cell Mol. Biol., March 1, 2000; 22(3): 265 - 271. [Abstract] [Full Text]
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G. P. ANDERSON Interactions between Corticosteroids and beta -Adrenergic Agonists in Asthma Disease Induction, Progression, and Exacerbation Am. J. Respir. Crit. Care Med., March 1, 2000; 161(3): S188 - 196. [Full Text] [PDF]
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A. Braun, M. Lommatzsch, A. Mannsfeldt, U. Neuhaus-Steinmetz, A. Fischer, N. Schnoy, G. R. Lewin, and H. Renz Cellular Sources of Enhanced Brain-Derived Neurotrophic Factor Production in a Mouse Model of Allergic Inflammation Am. J. Respir. Cell Mol. Biol., October 1, 1999; 21(4): 537 - 546. [Abstract] [Full Text]
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A. Kaser, S. Dunzendorfer, F. A. Offner, T. Ryan, A. Schwabegger, W. W. Cruikshank, C. J. Wiedermann, and H. Tilg A Role for IL-16 in the Cross-Talk Between Dendritic Cells and T Cells J. Immunol., September 15, 1999; 163(6): 3232 - 3238. [Abstract] [Full Text] [PDF]
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B. N. Lambrecht, I. Carro-Muino, K. Vermaelen, and R. A. Pauwels Allergen-Induced Changes in Bone-Marrow Progenitor and Airway Dendritic Cells in Sensitized Rats Am. J. Respir. Cell Mol. Biol., June 1, 1999; 20(6): 1165 - 1174. [Abstract] [Full Text]
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M. Korsgren, C. G.A. Persson, F. Sundler, T. Bjerke, T. Hansson, B. J. Chambers, S. Hong, L. Van Kaer, H.-G. Ljunggren, and O. Korsgren Natural Killer Cells Determine Development of Allergen-induced Eosinophilic Airway Inflammation in Mice J. Exp. Med., February 1, 1999; 189(3): 553 - 562. [Abstract] [Full Text] [PDF]
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