The Immunotoxicology Group has initiated studies pertaining to the role of the pulmonary Immune system in the pathogenesis of lung diseases. The objectives of these studies Include (1) to evaluate the potential adverse effects of inhaled agents on lung immunity - specifically lung macrophages and lung interstitial lymphocytes: (2) If possible, to examine potential mechanisms of toxicity: and (3) to relate these observed changes in immune function to clinicians and regulatory agencies so that improved treatment and monitoring may be facilitated. Studies were performed in the following areas: (1) descriptive lung immuno- toxicity studies following exposure to asbestos: and (2) mechanistic studies on the role of specific cell types in the pathogenesis of asbestos related lung disease. The results of these studies demonstrate that brief exposure to chrysotile asbestos produces a marked and sustained suppression Of pulmonary natural killer cell activity. This suppression in cytotoxicity is not due to an impairment in the function of these cells but an actual depletion of these cells within the interstitial compartment. This suppression of NK cell numbers can be reversed with interferon Inducers, suggesting that asbestos is causing an impairment in the normal cellular signals responsible for NK cell turnover within the lung. Also underway are studies examining the role of T cells in asbestos induced fibrosis and inflammation. By exposing animals genetically deficient in T lymphocytes (nude mice), these studies have shown that nude mice develop a greater inflammatory response to asbestos as well as a more severe fibrotic response, suggesting that T lymphocytes play a protective role in asbestos induced lung injury.
