Association of Activated Cytolytic Lung Lymphocytes with Response to Prednisone Therapy

Association of Activated Cytolytic Lung Lymphocytes with Response to Prednisone TherapyPrevious studies have suggested that immune mechanisms may participate in the pathogenesis of certain interstitial lung diseases (eg, IPF, sarcoidosis, and hypersensitivity pneumonitis). While these diseases may have different initiating events and intermediate phases, they share a common final pathway leading to fibrosis and pulmonary insufficiency. IPF is characterized by accumulation of inflammatory cells in the lung, destruction of normal alveoli, and fibrosis. In contrast to sarcoidosis and hypersensitivity pneumonitis, IPF has not been thought to involve a local cell-mediated response. For example, sarcoidosis and hypersensitivity pneumonitis patients are known to have T-cell alveolitis with an altered distribution of lymphocyte subsets, but in IPF, lymphocyte subset ratios have been reported to be normal by Hunninghake and Crystal and to be decreased by Izumi et al. Link

Caution must be exercised in interpreting lymphocyte phenotyping data to characterize the functional properties of local immunocompetent cells, since both CD4 4- and CD8 -I- T-lymphocytes can have diverse activities. An alternative approach to studying the immunologic components of these interstitial lung diseases therefore has been to examine the functional activity of lymphocytes in BAL fluid. Increased levels of proliferative activity, lymphokine secretion, and NK activity have been observed from BAL fluid lymphocytes of patients with sarcoidosis. In contrast, activated lymphocytes have not been detected in the BAL fluid of IPF patients.
In this study, we investigated the cytolytic activity of lymphocytes from BAL fluid and from peripheral blood of patients with IPF. To measure the level of cytolytic lymphocyte activity, we used a standard lectin-dependent cell-mediated cytotoxicity assay. This assay permits the detection of specific cytolytic cells and interleukin-2 (IL-2)-activated killer cells (IAK), but it does not detect NK cells. The lectin-dependent assay was employed because it is unknown which antigen(s) may be involved in the pathogenesis of IPF. The data obtained in this report demonstrated a subgroup of IPF patients with elevated lectin-dependent killing in BAL fluid. Longitudinal studies of these patients demonstrated an association between improved pulmonary function and decreased lectin-dependent cytolytic activity following prednisone therapy.

Category: Pulmonary Fibrosis

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