Activated memory T helper cells in bronchoalveolar lavage fluid from patients with atopic asthma: relation to asthma symptoms, lung function, and bronchial responsiveness.

Abstract

BACKGROUND: Bronchial mucosal inflammation and epithelial damage are characteristic features of asthma. Activation of T helper lymphocytes may contribute to this process by mechanisms including the release of cytokines promoting eosinophil infiltration and activation. METHODS: Bronchial washings and bronchoalveolar lavage fluid were obtained from 29 atopic asthmatic patients (19 with current symptoms and 10 symptom free) and 13 normal volunteers. Flow cytometry was used to assess T cell phenotype and activation status in bronchoalveolar lavage fluid and peripheral blood, and differential cell counts were made on bronchial washings and bronchoalveolar lavage fluid. Findings were related to severity of disease as reflected by symptom scores, baseline lung function, and airway responsiveness. RESULTS: CD4 T lymphocytes in bronchoalveolar lavage fluid and blood from asthmatic patients were activated by comparison with controls (CD4 CD25, median 16.8% v 8.7% for bronchoalveolar lavage fluid, and 15.3% v 8.7% in blood). Bronchoalveolar lavage fluid CD4 T cells from both asthmatic patients and controls were of memory phenotype (95.8% and 96.8% CD45RO and 1.7% and 0.4% CD45RA respectively), whereas both CD45RO and CD45RA T cells were present in blood. Patients with asthma and current symptoms showed increased bronchoalveolar T cell activation compared with patients without symptoms (CD4 CD25 18.7% v 12.3%). Within the asthmatic group there was a significant association between CD4 CD25 lymphocytes and asthma symptom scores (rs = 0.75), airway methacholine responsiveness (log PC20, rs = -0.43) and baseline FEV1 (rs = -0.39). A correlation was also found between CD4 CD25 lymphocytes and eosinophils in bronchoalveolar lavage fluid (rs = 0.48). Eosinophils in bronchoalveolar lavage fluid were increased in asthmatic patients compared with controls and the percentage of eosinophils in bronchoalveolar lavage fluid correlated with asthma symptom score. A relation was found between percentage of epithelial cells in bronchoalveolar lavage fluid and FEV1 and methacholine PC20. CONCLUSION: These results support the hypothesis that selective activation of memory CD4 T cells contributes to eosinophil accumulation, bronchial hyperresponsiveness, and symptoms in asthma.