title: Sensitivity to bleomycin-induced lung injury is not moderated by an antigen-limited T-cell repertoire.
abstract: Pulmonary fibrosis is a progressive scarring disease of the lung. It has been suggested that fibrosis is an inflammatory process, and cytokines such as tumor necrosis factor (TNF)-alpha and transforming growth factor (TGF)-beta have been shown to play key roles in the pathogenesis of fibrotic lung disease. However, the source of these cytokines remains in question and there is controversy over the role that infiltrating inflammatory cells play in fibrosis. T cells could play a key role by releasing cytokines upon engaging autoantigens revealed as a result of necrosis or apoptosis following epithelial injury. Some studies have shown that disrupting T-cell function leads to more severe disease, whereas others have shown that T-cell deficiency protects against fibrotic injury. To investigate whether specific antigen engagement by T cells is required for the development of fibrosis, bleomycin was instilled into the lungs of mice expressing a transgenic T-cell receptor beta (TCRbeta) gene. Expression of the TCRbeta transgene prevents effective recognition of antigens other than a single epitope of hen egg lysozyme. These mice therefore have defective antigen-specific responses but a normal representation of mature T-cell subsets. If antigen-specific T-cell engagement is required for the development of lung fibrosis, bleomycin-induced fibrosis should be reduced in the TCRbeta transgenic mice. In fact, there is no difference in the inflammatory or fibrotic response to bleomycin between TCRbeta transgenic and control mice. Thus, if T cells are required for fibrogenesis, it must involve an antigen-independent mechanism.
authors.affiliation: Department of Microbiology and Immunology, Division of Pulmonary and Critical Care Medicine, University of Rochester, Rochester, New York 14642, USA. thomas_thatcher@urmc.rochester.edu
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Thatcher
authors.forename: Patricia J
authors.initials: PJ
authors.lastname: Sime
authors.forename: Richard K
authors.initials: RK
authors.lastname: Barth
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000941:Antigens / Q000235:genetics; D001761:Bleomycin / Q000633:toxicity*; D002645:Chickens; D019674:Genes, T-Cell Receptor beta; D008168:Lung / Q000187:drug effects* / Q000276:immunology*; D055370:Lung Injury; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009113:Muramidase / Q000235:genetics / Q000276:immunology; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology*
chemical_list: D000941:Antigens; D001761:Bleomycin; D009113:Muramidase