Experimental hypersensitivity pneumonitis: lack of tolerance.

Abstract

Most subjects repetitively exposed to agents responsible for hypersensitivity pneumonitis (HP) do not develop persistent or progressive pulmonary inflammation. To determine if immunologic tolerance is associated with resolution of pulmonary abnormalities despite continuing exposure, we examined markers of local immunologic reactivity in a model of HP in rabbits. Rabbits were exposed to Micropolyspora faeni (M. faeni), the agent responsible for farmer's lung disease, with 3 sensitizing and 2, 4, or 8 challenge intratracheal injections. We determined bronchoalveolar macrophage migration inhibition (MMI) induced by M. faeni antigen, mitogen, and antigen-induced lymphocyte proliferation of lymphocytes derived from the lungs and hilar lymph nodes, and the amount of IgG antibody to M. faeni in serum and bronchoalveolar lavage fluid. We found MMI of lavage cells from rabbits exposed to M. faeni. Migration inhibition was dependent on ongoing protein synthesis. Hilar node and pulmonary lymphocytes proliferated upon exposure to M. faeni antigen, and anti-M. faeni antibody was found in serum and lavage fluid from M. faeni-treated rabbits. There were no differences between rabbits challenged 2, 4, and 8 times. We conclude that resolution of pulmonary histologic abnormalities in this model of hypersensitivity pneumonitis is not associated with evidence of immunologic tolerance.