The long-term objective of this research project is to understand the role of a subpopulation of lymphocytes in the generation of lung injury, particularly as it pertains to the bone marrow transplant population.
The specific aims of this project are to gain insight into lymphocyte homing to lung and the mechanisms by which these cells generate an inflammatory response localized to lung. The research design that we will use to achieve these aims will involve the study of a Th1 cell clone, a cell type known to be crucial in the generation of graft versus host disease. We will attempt to block localization of these cells in lung by inhibiting leukocyte adhesion with monoclonal antibodies, specific chemical inhibitors and transgenic mice deficient in adhesion molecules. We will investigate the mechanisms by which these cells generate a localized response by studying the elaboration of inflammatory mediators (chemokines) that have relevance to leukocyte recruitment.