Pulmonary and systemic immunoregulatory changes during the development of experimental asbestosis

Initial studies on the effects of low dose exposure to asbestos on pulmonary and systemic immune responses have revealed a bi-phasic pattern characterized by an early enhancement followed by inhibition of lymphocyte responses to several mitogens. In the present study, we sought to define the cellular and humoral factors, responsible for the observed effects. The early enhancement of peripheral blood and pulmonary lymphocyte responses to mitogens may be due, at least in part, to the loss of the inhibitory capacity of alveolar macrophages from asbestos exposed animals to suppress lymphocyte response. Furthermore, macrophages from low dose exposed animals actually enhanced lymphocytes responses to Con A and PHA. The latter inhibition observed following 6-12 months of exposure may be due to the in vivo generation of suppressor lymphocytes. Unfractionated lymphocytes from blood or alveolar space as well as enriched T cells from high dose exposed animals suppressed the proliferative responses of pulmonary or circulating lymphocytes to PHA and Con A, but not to PWM. Similarly, pre-incubation of normal blood or pulmonary lymphocytes in serum from high dose exposed animals for 24 h induced the appearance of suppressor cell activity in these populations when further tested in a co-culture assay with normal fresh lymphocytes. Taken together, these studies demonstrate the multi-faceted effects of asbestos on the immune system. The eventual fibrogenic process of asbestosis may result from the interplay of several mechanisms, some of which are suggested in this work.