Activated CD8+ T cells and natural killer T cells in bronchoalveolar lavage fluid in hypersensitivity pneumonitis and sarcoidosis.

BACKGROUND: Sarcoidosis and hypersensitivity pneumonitis are diffuse parenchymal lung diseases characterized by formation of non-caseating granulomas with a bronchocentric distribution. Analysis of the white blood cell differential profile in bronchoalveolar lavage fluid can be a useful supplement in the diagnostic work-up. OBJECTIVE: Diagnostic markers that can improve the discrimination of sarcoidosis and hypersensitivity pneumonitis are wanted. METHODS: Bronchoalveolar lavage fluid fractions of CD4+ and CD8+ T cells expressing the activation marker HLA-DR and fractions of natural killer T cells determined by flow cytometry were investigated in sarcoidosis (N=83), hypersensitivity pneumonitis (N=10) and healthy control subjects (N=15). RESULTS: In hypersensitivity pneumonitis, natural killer T cell fractions were over 7-fold greater [median (IQR): 5.5% (3.5-8.1) versus 0.7% (0.5-1.2), p<0.0001], and HLA-DR+ fractions of CD8+ lymphocytes were almost two fold greater [median (IQR): 79% (75-82) versus 43% (34-52), p<0.0001] than in sarcoidosis. In healthy control subjects, natural killer T cell fractions of leucocytes and HLA-DR+ fractions of CD8+ lymphocytes were lower [median (IQR): 0.3% (0.3-0.6) and 30% (26-34), p=0.02 and p=0.01 compared to sarcoidosis]. The combined use of these two markers seems to discriminate the diseases very well. CONCLUSION: This study suggests a role for the bronchoalveolar lavage fluid lymphocyte subsets HLA-DR+ CD8+ T cells and natural killer T cells in the diagnostic work up of sarcoidosis and hypersensitivity pneumonitis.

Activated CD8(+) T cells and NKT cells in BAL fluid improve diagnostic accuracy in sarcoidosis.

PURPOSE: The clinical diagnosis of pulmonary sarcoidosis is based on the presence of noncaseating granulomas in an appropriate clinical setting with either bilateral hilar adenopathy and/or parenchymal infiltrates. Lymphocytosis with an increased CD4/CD8 T cell ratio in bronchoalveolar lavage fluid is supportive. We evaluated the diagnostic accuracy of a predictive binary logistic regression model in sarcoidosis based on sex, age, and bronchoalveolar lavage fluid cell profile with and without the inclusion of HLA-DR(+) CD8(+) T cells and natural killer T-cell fractions. METHODS: A retrospective analysis of differential cell counts and lymphocyte phenotypes by flow cytometry in bronchoalveolar lavage was performed in 183 patients investigated for possible diffuse parenchymal lung disease. A logistic regression model with age, sex, lymphocyte fraction, eosinophils, and CD4/CD8 ratio in bronchoalveolar lavage fluid (basic model) was compared with a final model, which also included fractions of HLA-DR(+) CD8(+) T cells and natural killer T cells. Diagnostic accuracy of the two models was assessed by receiver operating characteristic (ROC) curves. RESULTS: The area under the ROC curve for the basic and final model was 0.898 [95 % confidence interval (CI) 0.852-0.945] and 0.937 (95 % CI 0.902-0.972), respectively, p = 0.008. CONCLUSIONS: Assessment of HLA-DR(+) CD8(+) T cell and natural killer T-cell fractions may improve diagnostic accuracy and further strengthen the importance of bronchoalveolar lavage in the diagnostic workup of sarcoidosis.