Altered nonspecific lymphocyte cytotoxicity in bronchoalveolar lavage of lung transplant recipients: can it be useful in monitoring rejection or infection?

Abstract

A reliable method for determining the adequacy of immunosuppression of the lung allograft and the absence of rejection or infection does not exist. The purpose of this study is to evaluate the potential role of bronchoalveolar lavage (BAL) in monitoring the adequacy of immunosuppression of lung allografts and in identifying the possible presence of acute rejection (AR) or infection. Thirty-one consecutive lung transplant recipients were subjected to bronchoscopy, transbronchial biopsy, and BAL either as routine surveillance or for decline in lung function (n=68 episodes: 27 normal, 17 infections, six grade IAR, 10 grade II-III AR, and eight obliterative bronchiolitis). Diagnosis was always confirmed histologically and by microbiological workup. Harvested cells underwent phenotypic analysis, and T lymphocytes were subjected to nonspecific lectin-dependent cell-mediated cytotoxicity (LDCMC) and natural killer cytotoxic assays. BAL from normal grafts predominantly contained macrophages (72.8+/-4.4%), with lower neutrophil (13.9+/-4.1%) and lymphocyte (13.2+/-2.2%) populations. Grade II-III AR and infection were associated with an increase in the percentage of neutrophils (43.3+/-8.3% and 33.2+/-3.6%, respectively, P=0.02). BAL of normal allografts contained T cells with low LDCMC (7.4+/-4.5%) and natural killer cytotoxicity (6.3+/-3.4%), whereas grade II-III AR was associated with a significant elevation in LDCMC (32.5+/-11.6%, P=0.019). Pulmonary infection, regardless of its type, was associated with significant elevation in BAL natural killer cytotoxicity (23.9+/-4.9%, P=0.033). Patients with obliterative bronchiolitis, on the other hand, had a mild elevation in the percentage of neutrophils and lymphocytes in BAL, which did not reach statistical significance. However, BAL T-cell LDCMC was significantly elevated (37.6+/-13.7%, P=0.019) compared with normal and infected allografts. We conclude that phenotypic and nonspecific cytotoxic T-cell analysis of BAL, when complimented with microbiological studies, may be useful in surveillance of lung transplant recipients and in determining whether allografts are likely to be quiescent, or possibly affected by acute/chronic rejection or infection, necessitating further definitive action.