Exposure of the lung to environmental agents that can cause occupational hypersensitivity pneumonitis (OHP) may result in either severe inflammation and organ dysfunction or in virtually no changes of normal pulmonary anatomy and physiology. There is wide unexplained variability among individuals in their response to inhalational antigenic exposure. We will use a well established animal model of active and adoptive OHP to test the hypotheses that: (1) suppressive influences project the lung against the effects of antigenic challenge; (2) administration of suppressor cells can prevent active and adoptive experimental OHP (EOHP); (3) administration of anti T cell or Ia antibody can prevent active and adoptive EOHP; (4) administration of attenuated T cell lines capable of transferring EOHP can prevent active and adoptive EOHP; and (5) T lymphocyte clones can be established form both bronchoalveolar lavage of both symptomatic subjects with Farmers' Lung Disease and asymptomatic exposed subjects.
Our specific aims are to: 1) establish guinea pig T cell lines capable of transferring adoptive EOHP; 2) determine if treatment with anti T cell antibody or anti-Ia antibody will prevent active EOHP; 3) determine if treatment with anti T cell antibody or anti-Ia antibody will prevent adoptive EOHP; 4) determine if administration of suppressor cells can prevent active or adoptive EOHP; 5) determine if administration of attenuated T cell lines can prevent active and adoptive EOHP; 6) determine if macrophages (peritoneal and alveolar) can act as accessory cells in the in vitro development of effector cells and if the origin (number of challenges) of the alveolar macrophages (AM) affects this capability; 7) establish and characterize T cell clones from bronchoalveolar lavage of farmers exposed to agents that cause Farmers' Lung Disease with and without symptoms. The results of this work is applicable to both HP and inhalational exposure to other airborne agents such as inorganic material and viable microorganisms (bacteria and viruses).
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