It has been postulated that alveolar macrophages play a crucial role in a variety of local immune processes in the lung. In this regard, it is known that the lung can generate and immune response to an antigen which is distinct from the systemic response. It is also clear that a variety of acute and chronic diseases of the lower respiratory tract are mediated by immune processes. One important means by which alveolar macrophage could play a role in these processes is via the presentation of antigen to lymphocytes. Prior studies, however, using alveolar macrophages from both human and animal sources, have not clearly identified the role of the alveolar macrophage in these local immune responses. In this regard, it has been demonstrated, in different studies, that alveolar macrophages can both augment and suppress antigen-induced immune responses. The purpose of the studies outlined in this proposal is to systematically evaluate the capacity of human alveolar macrophages to present antigen to autologous lymphocytes. In our study of normal macrophages, we will define the different culture conditions which are necessary for these macrophages to present antigen to lymphocytes as well as conditions which permit these cells to suppress these immune processes. As a part of the evaluation of the capacity of alveolar macrophages to present antigen, we will also evaluate these cells for the presence of surface Ia antigen and their ability to release interleukin 1. Once the culture conditions have been identified which permit macrophages to help or suppress antigen-induced immune responses, we will also determine whether these effects of macrophages are mediated, in part, by the generation of helper and suppressor T-lymphocytes. In addition, we will evaluate alveolar macrophages from patients with tubercolosis to determine if these activated macrophages are more efficient in presenting antigen that are normal macrophages. If there is a difference between normal macrophages from patients with tuberculosis, we will attempt to activate normal macrophages by exposure to lymphokines and/or muramyl dipeptide. These studies should enhance our understanding of the role of alveolar macrophages in mediating local immune responses in the lung.
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