Human alveolar macrophage regulation of lymphocyte proliferation

Human alveolar macrophages obtained by bronchoalveolar lavage have different accessory cell characteristics than do autologous, peripheral-blood-derived macrophages for the support of lymphocyte proliferative responses. To further investigate these differences, we performed mixing experiments in which variable numbers of the 2 macrophages were cocultured and assayed for support of mitogen-(phytohemagglutinin; PHA) and antigen-(streptokinase-streptodornase; SK-SD) stimulated proliferation of purified autologous lymphocytes. Alveolar macrophages promoted greater lymphocyte proliferation, in proportion to their added number in coculture with peripheral-blood-derived macrophages, when using a suboptimal concentration of PHA. In contrast, even small numbers of alveolar macrophages suppressed lymphocyte proliferation supported by peripheral-blood-derived macrophages when using the optimal concentration of PHA or the antigen SK-SD. The data indicated that diminished support exhibited by alveolar macrophages for optimal mitogen-stimulated or antigen-stimulated lymphocyte responses was due to active suppression by the cells, rather than to deficient or defective accessory cell function. Thus, alveolar macrophages have regulatory effects on lymphocyte proliferation that are dependent on type and concentration of mitogenic stimulation. Such regulation may relate to alveolar macrophage function in vivo, providing appropriate response yet limiting inflammation in the lung.