Immunoregulatory functions of BCG-elicited alveolar macrophages in cell-mediated immune responses

The pulmonary alveolar macrophage (AM) has been shown to play an important role in maintenance of the lung. However, the function of AM in specific cell-mediated immune responses has not been studied in detail. By employing both functional and immunologic assays, the present studies were undertaken to investigate the accessory and immunoregulatory functions of BCG-elicited AM in cell-mediated immune responses in vitro. AM, at concentrations of from 1.0 to 10%, could replace the accessory function of splenic adherent cells in the biological and functional activation of purified T-lymphocyte populations stimulated by mitogen and allogeneic cells as well as for the generation of cytotoxic effector cells. In unfractionated lymphoid cell cultures, AM were found to exert pronounced dose-dependent suppressive effects on mitogen and allogeneic cell stimulation. AM-mediated suppression of cell-mediated immune responses required metabolically active AM, but it did not require direct physical contact between AM and the stimulated lymphocytes. Furthermore, kinetic studies suggested that AM-mediated suppression was a time-dependent event that affected the afferent phase of T-cell activation by arresting the development of a primary activation signal. Moreover, the biological manifestation of suppression was characterized by inhibition of blast transformation, a decline in interleukin-2 receptor expression, as well as decreased proliferation and differentiation of precursors into effector cells (cytotoxic T-lymphocytes). These results suggest that BCG-elicited AM are capable of both accessory and regulatory functions in cell-mediated immunity.