Regulatory Role of Gama-Delta T cells in the Development of Pulmonary Fibrosis

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DESCRIPTION (provided by applicant): This proposal describes a 5 year training program for the development of an academic career Pulmonary Sciences, Critical Care Medicine and Immunology. The principal investigator has completed structured fellowship in Pulmonary and Critical Care Medicine at the University of Colorado. He expand his scientific skills through integration of interdepartmental resources. This program will promote the in-depth understanding of immunology as applied to pulmonary Drs. Fontenot and O'Brien will both serve as mentors for the principal investigator's scientific development. Dr. Fontenot is a highly regarded expert in T cell-mediated lung disease. Dr. O'Brien is recognized international leader in v5 T cell research. Together, Drs. Fontenot and O'Brien have trained numerous clinician scientists, postdoctoral fellows and graduate students. In addition, an advisory committee highly-regarded scientists in the fields of interstitial lung disease will provide scientific and career Research will focus on the mechanisms by which ap T cells promote while y5 T lymphocytes development of pulmonary fibrosis. Recent work in the laboratory has demonstrated that mice repeatedly inhale the Gram-positive microorganism, Bacillus subtilis, develop large numbers of and y5 T cells in the lung and pulmonary fibrosis. The proposed experiments are designed to examine role of each T cell subset in the generation of pulmonary fibrosis using adoptive transfer techniques transgenic mice with T cell receptor targeted deletions. Subsequently, the mechanisms by which cell subset promotes or delays the development of pulmonary fibrosis will be investigated using in vivo and vitro cellular techniques. The specific aims include: 1. Determe if ap T cells promote deposition in the lungs of mice repeatedly exposed to B. subtilis and 2. Delineate the immunoregulatory role of v5 T cells in this murine model of hypersensitivity pneumonitis and pulmonary fibrosis. This the first detailed investigation of the role of different T cell subsets in the generation of pulmonary The University of Colorado and National Jewish Medical Research Center through their strong and Integrated Department of Immunology provides young investigators a fertile environment to highest level of basic science research from which to build an independent academic career. (End of Abstract)