Published ahead of print on August 11, 2004, doi:10.1164/rccm.200404-464OC
© 2004 American Thoracic Society doi: 10.1164/rccm.200404-464OC
CD4 T Lymphocyte–mediated Lung DiseaseSteady State between Pathological and Tolerogenic Immune ReactionsDepartment of Cell Biology and Immunology, German Research Center for Biotechnology, Braunschweig; Department of Pathology, School of Veterinary Medicine, Hannover; Institute of Medical Microbiology, Hannover Medical School, Hannover, Germany; and Yale University School of Medicine, New Haven, Connecticut Correspondence and requests for reprints should be addressed to Dunja Bruder, Ph.D., Department of Cell Biology and Immunology, German Research Centre for Biotechnology, Mascheroder Weg 1, D-38124 Braunschweig, Germany. E-mail: dbr{at}gbf.de Although considerable evidence indicates a role for CD4+ T lymphocytes (T cells) in airway inflammation, little data exist regarding the mechanisms underlying the induction and regulation of CD4+ T cell reactivity to lung-specific antigens. To dissect the immunologic and molecular mechanisms of CD4+ T cell dysregulation, reactivity to a self-antigen expressed in the lung of mice bearing a major histocompatibility complex class-II-restricted T cell receptor specific for this antigen was studied. Transgenic mice developed 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 older mice with prominent formation of lymphoid follicles but reduced interstitial infiltration. Extensive immunologic characterization of self-reactive CD4+ T cells isolated from the inflamed lung suggested the induction of regulatory T cells in the site of inflammation. Moreover, inflammation was accompanied by broad changes in the gene expression pattern toward a profile partially resembling that of activated, but strikingly, also that of regulatory CD4+ T cells. Together our data provide important insights into functional and molecular alterations being associated with the induction and/or regulation of T cell-mediated pulmonary inflammation.
Key Words: airway inflammation • mucosal self-antigen • peripheral tolerance • transgenic mice This article has been cited by other articles:
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