Acute allograft rejection is unfortunately common following clinical lung transplantation. Importantly, acute rejection has been repeatedly identified as the principal risk factor for the development of bronchiolitis obliterans which is the clinical manifestation of chronic lung graft rejection. Bronchiolitis obliterans or chronic rejection is the major risk factor for poor prognosis and continues to be the main obstacle for further improvement of long-term survival following lung transplantation. Acute allograft rejection is mediated by inflammatory cytokines and chemokines that can be altered by gene transfer of Transforming Growth Factor B1 (TGF B1). T lymphocytes are the major effectors of acute rejection. Our hypothesis is that TGF B1 alters the cytokine balance favoring an anti-inflammatory environment and inhibits chemokine induced T lymphocyte recruitment and proliferation. The long-term goal of this project is to investigate the mechanisms by which early anti- inflammatory gene expression of TGF B1 reduces acute allograft rejection with the eventual goal of improving clinical lung transplantation.
