title: Alveolar macrophage immunosuppression is maintained in rabbit models of hypersensitivity pneumonitis.
abstract: 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 lymphocyte blastogenesis in rabbit models of acute and chronic hypersensitivity pneumonitis, desensitized animals, and control animals. We found that 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 partially 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.
authors: Department of Internal Medicine, University of Iowa, College of Medicine, Iowa City.
authors: W C
authors: WC
authors: Kopp
authors: M T
authors: MT
authors: Suelzer
authors: H B
authors: HB
authors: Richerson
mesh_terms: D000542:Alveolitis, Extrinsic Allergic / Q000276:immunology*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002458:Cell Fractionation; D000939:Epitopes; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008264:Macrophages / Q000276:immunology*; D011650:Pulmonary Alveoli / Q000276:immunology* / Q000473:pathology; D011817:Rabbits
chemical_list: D000939:Epitopes; D007213:Indomethacin