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

Abstract

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.