Differential Rates of Apoptosis in Bronchoalveolar Lavage and Blood of Lung Transplant Patients

Abstract

Lung transplant tolerance depends on effective control of T-cell proliferation and activation. Commonly used immunosuppressive agents promote peripheral blood-derived lymphocyte apoptosis and inhibit production of cytokines involved in lymphocyte proliferation and survival. However, there have been no studies of the effectiveness of immunosuppressive treatments on apoptosis of T cells derived from the airways of lung transplant recipients. Our main aim was to compare apoptosis of T cells derived from peripheral blood and bronchoalveolar lavage (BAL) from lung transplant recipients, with no evidence of chronic or acute cellular rejection, and healthy volunteers. Lung transplantation may also be associated with increased apoptosis of airway epithelial cells. To investigate this possibility, we also examined apoptosis of epithelial cells derived from bronchial brushing. BAL, blood, and bronchial brushings were obtained from lung transplant recipients (n = 9) and age-matched controls (n = 15). T cell and epithelial cell apoptosis, Fas, Bax, Bcl-2, and p53 were evaluated by flow cytometry. Increased apoptosis of peripheral blood T cells and decreased Bcl-2 were observed in the transplant patients. In contrast, there was no significant change in apoptosis of airway T cells or apoptosis-related proteins. Increased apoptosis and increased p53 were observed in the airway epithelial cells from the transplant recipients, possibly as a result of ineffective control of infiltrating cytotoxic T cells. Immunosuppressive agents may not be as effective in inducing apoptosis of airway-derived T cells as peripheral blood-derived T cells after lung transplantation. These findings may have implications on the outcome of the immune response in the airways after immunosuppressive therapy and may be particularly relevant to lung allograft rejection.