Published ahead of print on August 11, 2004, doi:10.1164/rccm.200404-464OC Am. J. Respir. Crit. Care Med., Volume 170, Number 11, December 2004, 1145-1152 A more recent version of this article appeared on December 1, 2004
Submitted on April 7, 2004 CD4 T Cell Mediated Lung Disease: Steady State between Pathological and Tolerogenic Immune ReactionsDunja Bruder1*,1 Department of Cell Biology and Immunology, German Research Centre for Biotechnology, Braunschweig, Germany, 2 Department of Pathology, School of Veterinary Medicine, Hannover, Germany, 3 Yale University School of Medicine, New Haven, CT, USA, 4 Department of Cell Biology and Immunology, German Research Centre for Biotechnology, Braunschweig, Germany; Institute of Medical Microbiology, Hannover Medical School, Hannover, Germany * To whom correspondence should be addressed. E-mail: dbr{at}gbf.de.
Although considerable evidence indicates a role for CD4+ 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 immunological and molecular mechanisms of CD4+ T cell dysregulation, reactivity to a self antigen expressed in the lung of mice bearing an MHC-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 immunological 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 towards 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: mucosal self-antigen, peripheral tolerance, airway inflammation, transgenic mice
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