CD4 T Lymphocyte-mediated Lung Disease: Steady State between Pathological and Tolerogenic Immune Reactions

• Published in: American journal of respiratory and critical care medicine 2004-12, Vol.170 (11), p.1145-1152
• Main Authors: Bruder, Dunja, Westendorf, Astrid M, Geffers, Robert, Gruber, Achim D, Gereke, Marcus, Enelow, Richard I, Buer, Jan
• Format: Article
• Language: English
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Antibodies; Antigens; Autoimmune Diseases - genetics; Autoimmune Diseases - immunology; Autoimmunity - genetics; Autoimmunity - immunology; Biological and medical sciences; Blood. Blood and plasma substitutes. Blood products. Blood cells. Blood typing. Plasmapheresis. Apheresis; CD4-Positive T-Lymphocytes - immunology; Chronic Disease; Connective tissue; Drug toxicity and drugs side effects treatment; Flow cytometry; Gene expression; Gene Expression Profiling; Genes, MHC Class II - genetics; Genes, MHC Class II - immunology; Hemagglutinins - genetics; Hemagglutinins - immunology; Inflammation; Influenza; Intensive care medicine; Lung diseases; Lung Diseases, Interstitial - genetics; Lung Diseases, Interstitial - immunology; Lungs; Lymphocytes; Medical sciences; Mice; Mice, Transgenic; Peptides; Pharmacology. Drug treatments; Pulmonary Surfactant-Associated Protein C - genetics; Pulmonary Surfactant-Associated Protein C - immunology; Sarcoidosis; Self Tolerance - genetics; Self Tolerance - immunology; T cell receptors; Toxicity: blood; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Transgenic animals
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/rccm.200404-464OC

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.