International Mammalian Genome Society

17th International Mouse Genome Conference

9-12 November 2003, Braunschweig, Germany


POSTER 80 - PATHOGENESIS OF CD4+ T CELL MEDIATED INFLAMMATION IN AN AUTOIMMUNE MOUSE MODEL OF PULMONARY DISEASE

Bruder D
German Research Centre for Biotechnology, Braunschweig, Germany

Co-Authors: 1) Westendorf AM., 1) Geffers R., 2) Gruber AD., 1) Buer J
Institutions: 1) German Research Centre for Biotechnology, Braunschweig, Germany, 2) School of Veterinary Medicine Hannover, Germany

To dissect the immunological and molecular mechanisms underlying autoimmune-mediated lung disease, CD4+ T cell reactivity to a lung-specific antigen was studied by transgenic expression of hemagglutinin (HA) in type II alveolar epithelial cells. Concomitant expression of HA and a MHC class II-restricted T cell receptor specific for HA in double transgenic mice resulted in the development of severe immune-mediated interstitial lung disease. Histological examination revealed a progressive interstitial pneumonitis characterized by massive lymphocytic and plasmacytic infiltration of interalveolar septa, a clinical picture closely resembling some of the interstitial lung diseases. Pulmonary inflammation reached a plateau state in elder mice with prominent formation of lymphoid follicles but reduced interstitial infiltration, suggesting the induction of peripheral tolerance mechanisms. Extensive immunological characterization of self-reactive CD4+ T cells isolated from the inflamed lung and global gene expression profiling suggested the induction of regulatory T cells in the site of inflammation. Moreover, inflammation was accompanied by brought changes in the gene expression pattern of lung-derived CD4+ T cells providing important insights to the pathobiology of pulmonary disease and offering potentially new molecular markers suitable for the detection and treatment of airway inflammation in human patients.


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