Involvement of human natural killer cells in asthma pathogenesis: Natural killer 2 cells in type 2 cytokine predominance

Abstract

T H 2 cells play a pivotal role in the pathogenesis of human asthma. Natural killer (NK) cells are also thought to divide into NK1 and NK2 subsets. Whether NK1 or NK2 cells are involved in asthma remains unclear. Triple-color flow cytometry for detecting intracellular cytokine and NK cell surface phenotype from asthmatic patients was used. The NK cell cloning and analysis with RT-PCR for cytokine expression and Western blotting for signal transducer and activator of transcription activation were performed. For the first time, we observed that the ratio of IL-4 + CD56 + NK2 cells in PBMCs of 8 asthmatic patients were higher than in healthy individuals. NK cell clones were then obtained by means of limited dilution, and the average mean of the relative intensity of PCR products for type 2 cytokines significantly increased in the asthmatic patients. Signal transducer and activator of transcription 6, a key transcript factor of type 2 phenotype, was constitutively activated in NK2 clones from asthmatic patients. We cocultured freshly purified NK cells from asthmatic patients with IFN-gamma and anti-IL-4 antibody in the presence of IL-15 and found that the content of IL-4 + NK2 cells significantly decreased after treatment. Interestingly, NK2-biased status in asthmatic patients was reversed when patients recovered from regular therapy. The results suggest that the NK2 cell subset is involved in the pathogenesis of asthma.