This project addresses immunological mechanisms that regulate chronic inflammation and remodeling in the respiratory tract. Mycoplasma pulmonis infection induces lifelong reorganization of the airway vasculature and mucosal epithelium and is a murine model of human chronic airway inflammation. Preliminary data suggest that M. pulmonis-related airway remodeling is regulated by T lymphocytes. The experiments in this proposal are designed to determine the mechanisms by which T cells regulate changes in the airways. The T cell response to M. pulmonis will be characterized and tested for its capacity to influence different aspects of airway remodeling. M. pulmonis-reactive T cells will be studied at the level of T cell receptor repertoire, cytokine phenotype and ability to induce immunopathology. Experiments will also address the physiological function of CD134, a member of the Tumor necrosis family of receptors that is prominently expressed on inflammatory T cells and which regulates the proliferation of T cells. These last experiments will focus on determining the mechanism by which CD134 influences T cell expansion and uncovering the circumstances in which CD134 function is most significant. These experiments will provide basic information about immunological mechanisms that influence the form and extent of airway remodeling in chronic airway inflammatory diseases. A better understanding of these mechanisms may suggest novel therapeutic targets and approaches for treating chronic airway disease.