Association of Activated Cytolytic Lung Lymphocytes with Response to Prednisone Therapy: Discussion

Numerous studies of cell-mediated immune phenomena in interstitial lung diseases have been reported. The role of activated cytolytic lymphocytes has not been previously investigated, despite the importance of these as major effector components of the immune response. Ours is the first report, to our knowledge, demonstrating the presence of activated cytolytic cells in the BAL fluid of some patients with IPF. Longitudinal studies indicated that this subgroup of IPF patients responded to prednisone therapy with improved pulmonary function, and, significantly, clinical improvement was associated with decreased lectin-dependent cytolytic lymphocyte activity in BAL fluid. Patients with cytolytic activity in peripheral blood but not in BAL fluid and patients without cytolytic activity from either source did not respond to prednisone therapy. Patients with IPF who had lectin-dependent activity in BAL fluid may constitute a subgroup who have more active inflammation or are in an earlier stage of disease then IPF patients without initial cytolytic activity.

We were able to study only a small number of IPF patients and therefore cannot make a reliable estimate of the prevalence of activated cytolytic lymphocytes in IPF patients. However, the striking and consistent correlation of positive CDCMC activity with steroid responsiveness, even in this small series, strongly suggests that the assay will be useful in assessing prognosis. Clinical parameters including BAL fluid cell contents and Ga scans were not consistently associated with improvement in pulmonary function in our group of IPF patients. Other investigators have reported that increased percentages of lymphocytes in BAL fluid correlated with subsequent clinical improvement. However, data from longitudinal studies of BAL cell content have not shown consistent correlations between these findings and the patients clinical course. In our study the initial percentage of lymphocytes did not consistently predict corticosteroid responsiveness. Two patients with increased percentages of lymphocytes had no response to treatment while the patient with the lowest percentage of lymphocytes had the most dramatic response to treatment. Link

Keough et al also reported that the percentage of neutrophils in BAL fluid decreased when IPF patients responded to corticosteroids. Neither Turner-Warwick and Haslam nor our study confirmed this finding. The lectin-dependent cytotoxicity assay detects specifically sensitized T-lymphocytes and IL-2 activated killer cell activity (IAK), but not NK cell activity. The finding of activated cytolytic lymphocytes in the lungs of some patients with IPF suggests that a cell-mediated immune response may occur in situ in this disorder. It is possible that cytolytic lymphocytes might be present in the lung of most patients with disease early in the course of the disorder. However, as patients usually present with advanced disease and pulmonary dysfunction, it is currently impossible to test this hypothesis. The data in this report does not permit assignment of the cytolytic activity to either specifically sensitized cytolytic T-cells or IAK cells. Though it is not possible to perform antigen-specific assays on these patients, future studies utilizing IAK-specific target cells will be useful in further defining the role of functional subsets of cytolytic lymphocytes in this disorder.
This report is the first, to our knowledge, to present data demonstration a cell-mediated immune response in the lungs of patients with IPF. Significant improvement in pulmonary function was observed in patients with lectin-dependent cytotoxicity in BAL fluid. Assays of activated cytolytic lymphocytes may, therefore, be useful in identifying IPF patients who have improved prognosis on immunosuppressive therapy.

Category: Pulmonary Fibrosis

Tags: bronchoscopy, lung lymphocytes, peripheral blood, pulmonary fibrosis, pulmonary function