ALVEOLAR MACROPHAGE IMMUNOSUPPRESSION IS MAINTAINED IN RABBIT MODELS OF HYPERSENSITIVITY PNEUMONITIS

[摘要] In established experimental models of hypersensitivity pneumonitis and, perhaps, in exposed, asymptomatic humans, continued aerosol exposure to protein antigen results in waning disease and a state of desensitization. The mechanisms causing such unresponsiveness are not well understood, but a possibility is enhanced immunosuppression by alveolar macrophages or other bronchoalveolar cells. Similarly, a loss of immunosuppressive function could result in the appearance of alveolitis. We therefore compared the ability of bronchoalveolar lavage (BAL) cells to augment or suppress antigen-specific lymphocytes blastogenesis in rabbit models of acute and chronic hypersensitivity pneumonitis, desensitized animals, and control animals. We found the BAL cells from all treatment groups suppressed antigen-specific lymphocyte blastogenesis at BAL:lymph node cell ratios of 1:1 to 1:8. BAL cells from some animals were suppressive at high BAL concentrations and, at lower concentrations, augmented the blastogenic response. Additional studies revealed no significant differences in the ability of mitomycin C-treated BAL cells to suppress or augment autologous lymphocyte blastogenesis at any ratio tested. Low-density, macrophage-enriched BAL cells obtained by Percoll fractionation maintained suppressive function. Addition of indomethacin to cultures only partialy abrogated BAL-mediated suppression of antigen-specific blastogenesis. We conclude that the development of alveolitis in this model cannot be attributed to loss, nor can desensitization be explained by augmentation, of alveolar macrophage immunosuppressive function.

[发布日期] 1988-08-01