Bronchiolitis Obliterans Syndrome Is Associated With Absence of Suppression of Peripheral Blood Th1 Proinflammatory Cytokines

Abstract

Bronchiolitis obliterans syndrome (BOS) is the single most important factor that limits long-term survival after lung transplantation. T cells are a major cell type involved in acute graft rejection; however, the role of these cells in BOS is unknown. There have been no previous studies of cytokine production by T cells from blood and bronchoalveolar lavage (BAL) and by intraepithelial T cells from bronchial brushings during BOS, and we hypothesized that proinflammatory cytokines may be increased during BOS despite standard immunosuppression regimes. To investigate the changes in intracellular cytokine profiles, whole blood, BAL, and bronchial brushings from stable lung transplant patients, those with BOS, and healthy controls were stimulated in vitro and intracellular cytokine production by CD8 (CD4) and CD8 T-cell subsets determined using multiparameter flow cytometry. There was a significant decrease in T-cell interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha in the blood of stable patients compared with patients with evidence of BOS. T-cell IFN-gamma and TNF-alpha was unchanged in the blood of BOS patients compared with healthy controls. T-cell TGF-beta was decreased in the blood of both patient groups compared with healthy controls and decreased in BOS compared with stable patients. There was an increase in BAL T-cell IFN-gamma and TNF-alpha in both patient groups compared with controls. BOS is associated with absence of immunosuppression of peripheral blood IFN-gamma and TNF-alpha T helper type 1 proinflammatory cytokines. Monitoring peripheral blood T-cell IFN-gamma and TNF-alpha may allow individual tailoring of immunosuppressive regimes to help reduce BOS in lung transplant patients.