Takashi Kinoshita1, Adrian Baatjes2, Steven G Smith2, Benny Dua2, Richard Watson2, Tomotaka Kawayama3, Mark Larche2, Gail M Gauvreau2, Paul M O'Byrne4. 1. Firestone Institute of Respiratory Health, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada; Department of Medicine, Division of Respirology, Neurology and Rheumatology, Kurume University, Fukuoka, Japan. 2. Firestone Institute of Respiratory Health, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada. 3. Department of Medicine, Division of Respirology, Neurology and Rheumatology, Kurume University, Fukuoka, Japan. 4. Firestone Institute of Respiratory Health, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada. Electronic address: obyrnep@mcmaster.ca.
Abstract
BACKGROUND: Natural regulatory T (Treg) cells are implicated in the regulation of the inflammatory response in patients with allergic asthma. OBJECTIVES: We sought to determine changes in Treg cell numbers in the airways and peripheral blood of isolated early responder (IER) versus dual responder (DR) subjects with mild allergic asthma before and after allergen challenge. METHODS: Induced sputum was collected from 22 subjects with allergic asthma (10 IERs and 12 DRs) and peripheral blood collected from 8 DRs with allergic asthma at 0, 7, and 24 hours after allergen challenge. Treg cells were identified by using fluorescently labeled antibodies to CD4 and forkhead box protein 3 and enumerated by using flow cytometry. RESULTS: There was a significant increase in the percentage of sputum CD4(+) cells 24 hours after allergen challenge in both IERs and DRs. The percentage of sputum Treg cells significantly decreased 24 hours after challenge in DRs but not IERs. This change was significantly correlated with the magnitude of the late asthmatic response. There was also a significant increase in the absolute number of sputum CD4(+) cells and Treg cells at 24 hours in DRs only. The ratio of the number of Treg cells to CD4(+) cells at 24 hours was significantly smaller in DRs compared with that in IERs. None of the above changes were observed in peripheral blood. CONCLUSIONS: DRs exhibit a diminished percentage of airway Treg cells after allergen challenge that is not observed in IERs and a significantly lower ratio of Treg cells to CD4(+) cells, which might contribute to the development of the late asthmatic response.
BACKGROUND: Natural regulatory T (Treg) cells are implicated in the regulation of the inflammatory response in patients with allergic asthma. OBJECTIVES: We sought to determine changes in Treg cell numbers in the airways and peripheral blood of isolated early responder (IER) versus dual responder (DR) subjects with mild allergic asthma before and after allergen challenge. METHODS: Induced sputum was collected from 22 subjects with allergic asthma (10 IERs and 12 DRs) and peripheral blood collected from 8 DRs with allergic asthma at 0, 7, and 24 hours after allergen challenge. Treg cells were identified by using fluorescently labeled antibodies to CD4 and forkhead box protein 3 and enumerated by using flow cytometry. RESULTS: There was a significant increase in the percentage of sputum CD4(+) cells 24 hours after allergen challenge in both IERs and DRs. The percentage of sputum Treg cells significantly decreased 24 hours after challenge in DRs but not IERs. This change was significantly correlated with the magnitude of the late asthmatic response. There was also a significant increase in the absolute number of sputum CD4(+) cells and Treg cells at 24 hours in DRs only. The ratio of the number of Treg cells to CD4(+) cells at 24 hours was significantly smaller in DRs compared with that in IERs. None of the above changes were observed in peripheral blood. CONCLUSIONS: DRs exhibit a diminished percentage of airway Treg cells after allergen challenge that is not observed in IERs and a significantly lower ratio of Treg cells to CD4(+) cells, which might contribute to the development of the late asthmatic response.
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