Cell mediated immune responses in the lung are pivotal in pulmonary defense and in hypersensitivity lung diseases. Antigen presenting cells are required both at the inductive stage and in the triggering of the effector limb of cell mediated responses. The goal of the proposed studies is to characterize the effective antigen presenting cell(s) in human lung and to investigate the cell-cell interactions which regulate the generation of immune responses in the lung. We propose that DC, located in airway epithelium, in BALT and in the interstitium are critical antigen presenting cells in the lung. Further, we propose that pulmonary macrophages interact with DC during the generation of immune responses. In some instances alveolar macrophages (AM) are suppressive cells; in other instances, they maintain or augment DC induced responses. Finally, we propose that natural killer (NK) cells suppress the generation of immune responses via a cytotoxic effect on DC. To evaluate the relative efficiency of DC, lung tissue macrophages and AM (from bronchoalveolar lavage) as antigen presenting cells, we will isolate all of these cells from the same starting pulmonary tissue preparation. The six specific objectives are: (1) To prepare a DC enriched population and a pulmonary macrophage enriched population from human lung tissue; (2) To develop a cytotoxic DC specific monoclonal antibody; (3) To compare the capacity of DC and tissue macrophages obtained from human lungs to stimulate antigen specific T cell responses by comparing their ability to stimulate allogeneic mixed leucocyte responses, autologous mixed leucocyte responses, secondary responses in immune individuals and primary immune responses in vitro. Additionally, we will determine whether AM can stimulate proliferation of T cell primed by DC; (4) We will determine whether human blood DC, human pulmonary DC, lung tissue macrophages and AM can serve as accessory cells for the generation of primary antibody forming cells; (5) Whether pulmonary DC interact with monocytes, AM, and lung tissue macrophages in the regulation of immune responses by evaluating the ability of these cells to alter DC induced T cell proliferation and antibody forming cell generation; and (6) Whether NK cells regulate the activity of accessory cells by evaluating whether depletion or addition of NK cells alters the ability of stimulator populations to generate a mixed leucocyte response.
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