Disordered pulmonary T-cell mediated immunity results in a variety of serious infections and inflammatory disorders in man. The broad goal of this proposal is to examine the mechanisms leading to antigen-specific pulmonary immunity in vivo. Specifically, we will determine how soluble and particulate antigens are handled by Ia+ pulmonary dendritic cells isolated from Lewis rats and investigate whether processed antigen is transported to local lymph nodes by motile Ia+ dendritic cells. The adherence of pulmonary dendritic cells to lung extracellular matrix protein will be determined. Factors modulating the motility of pulmonary dendritic cells will be investigated. The frequency of antigen-specific T cells in the lung following primary antigen-sensitization and following a secondary pulmonary antigen challenge will be determined. We shall address whether T-""""""""memory"""""""" cells are specifically entrapped in the lung and whether Ia+ dendritic cells in the pulmonary interstitium and the lung microvasculature present antigen directly to labelled memory T-cell clones in vivo. These experiments will greatly promote our current understanding of how antigen-specific cell mediated immunity is generated in the lung.
