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Association of activated cytolytic lung lymphocytes with response to prednisone therapy in patients with idiopathic pulmonary fibrosis.

Previous studies have suggested that immunologic mechanisms may contribute to pathogeneic reactions in certain interstitial lung diseases. Cytolytic lymphocytes are major effector cells of the immune response that have not been extensively studied in these disorders. To investigate the role of activated cytolytic lymphocytes in IPF, we studied B-cell and monocyte/macrophage-depleted lymphocyte preparations isolated from BAL fluid and peripheral blood of patients with this disease (n = 10) and used a lectin-dependent cytotoxicity assay to detect activated cytolytic lymphocytes. In longitudinal studies, those patients who had cytolytic activity of BAL fluid lymphocytes (range, 8 to 35 percent, n = 4) showed significant improvement in pulmonary function (mean increase in diffusing capacity, 30 +/- 2 percent) in association with decreased BAL fluid cytolytic lymphocyte activity after prednisone treatment. In contrast, patients who initially lacked cytolytic activity in BAL fluid (n = 6) did not improve with prednisone. Activated cytolytic lymphocytes were not observed in the BAL fluid of healthy subjects. These investigations suggest a causal relationship between activated cytolytic lymphocytes in the lung and disease activity in IPF and that assays of activated cytolytic lymphocytes are helpful in identifying patients who will improve with immunosuppressive therapy.