MECHANISMS OF HEMOSTASIS AND REPAIR IN THE LUNG

University Of California Davis, Davis CA

Investigators

Linked publications & trials

Abstract

DESCRIPTION (provided by applicant): The functions of gamma delta T lymphocytes in pulmonary epithelia are poorly understood. They probably mediate immune responses in the mucosa since they secrete cytokines, chemokines and epithelial growth factors. Our hypothesis is that sequential recruitment of distinct subpopulations of gamma delta T lymphocytes into the lungs at sites of epithelial cell damage is essential in maintaining pulmonary homeostasis and regulating epithelial repair. The following 2 specific aims will test this, and determine the functions of gamma delta T cells. 1. The sequential localization and quantification of subclasses of gamma delta T cells will be determined within normal, damaged and repairing pulmonary epithelia after exposure to either ozone or N. asteroides. 2. The modulation and regulation of gamma delta T lymphocytes will be studied using sequential reconstitution of characterized subpopulations of gamma delta T lymphocytes into the lungs of knockout mice. Two models of pulmonary injury will be used in normal and gamma delta T cell deficient mice to correlate specific attributes of gamma delta T cell function with the mechanisms for maintaining lung mucosal integrity. Comparing and contrasting the roles of gamma delta T cells in each model will help to elucidate the nature of their recognition and regulation of homeostasis and repair. Subsets of gamma delta T cells will be selected and reconstituted into gamma delta T cell deficient mice. These studies will be accomplished by a combination of flow cytometry, laser scanning cytometry, tissue microarrays, cell sorting, and quantitative morphometry. The goal of this research is to reveal those attributes of gamma delta T cell function that contribute to epithelial integrity, and when breached determine the beneficial levels of inflammation and repair.