Selective early increases of bronchoalveolar CD8+ lymphocytes in a LEW rat model of hypersensitivity pneumonitis.

ABSTRACT

BACKGROUND: The pathogenesis of hypersensitivity pneumonitis (HP) involves cell-mediated hypersensitivity; various bronchoalveolar T-cell subsets with uncertain roles in disease have been reported and implicated in the pathogenesis. OBJECTIVES: Previous studies at 72 hours after initial antigen challenges showed proportionate increases in T-cell phenotypes. Therefore we tested the hypothesis that early events in response to inhaled antigen in a LEW rat model of HP would include a disproportionate appearance in bronchoalveolar lavage fluid (BALF) and lung parenchyma of a specific T-effector cell responsible for subsequent inflammation and that these events could be identified by phenotyping. METHODS: We double labeled BALF and parenchymal lung lymphocytes with monoclonal antibodies and used flow cytometry to quantitate CD4+ and CD8+ phenotypic subsets 4 and 24 hours after inhalation of antigen. RESULTS: We found disproportionate increases in BALF CD8+ phenotypes. The strongest correlation with pathologic findings was for a putative cytotoxic effector (CD8+CD45R-) T lymphocyte. CONCLUSION: Meaningful interpretation of lung T-cell phenotype quantitation requires studies of kinetics of cellular influxes, timing after antigen challenge, and relative comparison with increases in other phenotypes. Any pathogenetic role assigned to a phenotype must also await functional studies, including cytokine generation and secretion and cell-cell interactions in situ.