Systemic and local lymphocyte responses in experimental hypersensitivity pneumonitis.

Abstract

The pathogenesis of hypersensitivity pneumonitis is incompletely understood; cell-mediated hypersensitivity mechanisms may be involved, but in vitro correlates have been studied in humans with inconclusive results. We used a rabbit model of hypersensitivity pneumonitis to study systemic and local antigen-specific lymphocyte responses as measured by in vitro incorporation of 3H-thymidine. Groups of animals were systemically immunized with ovalbumin and acutely or repeatedly challenged with aerosolized ovalbumin. Lymphocyte responses were measured in peripheral blood, mediastinal and popliteal lymph nodes, bronchus-associated lymphoid tissue, and bronchoalveolar wash fluids in these groups and in appropriate control animals. Lymphocyte proliferative responses to specific antigen, shown previously to be a T-cell response in this system, occurred after systemic or inhalation exposure to antigen. Acute alveolitis was associated with a decrease in peripheral blood lymphocyte responses and the presence of responsive lymphocytes in bronchoalveolar was fluids. Repeated inhalation challenge thrice weekly for 1 month, with waning of alveolitis, was not associated with significant changes in lymphocyte responsiveness. Antigen-specific lymphocyte blastogenesis did not define animals capable of developing alveolitis after aerosol challenge and did not appear, therefore, to distinguish effector cell activity in this model.