Alveolar macrophage immunosuppression is maintained in rabbit models of hypersensitivity pneumonitis.
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.
Kopp
W C
WC
Department of Internal Medicine, University of Iowa, College of Medicine, Iowa City.
Suelzer
M T
MT
Richerson
H B
HB
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
D000939:Epitopes; D007213:Indomethacin