Natural regulatory T cells in isolated early responders compared with dual responders with allergic asthma

• Published in: Journal of allergy and clinical immunology Vol. 133; no. 3; pp. 696 - 703
• Main Authors: Kinoshita, Takashi, MD, Baatjes, Adrian, MSc, Smith, Steven G., PhD, Dua, Benny, MSc, Watson, Richard, BSc, Kawayama, Tomotaka, MD, Larche, Mark, PhD, Gauvreau, Gail M., PhD, O’Byrne, Paul M., MD, FRCPI
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.03.2014; Elsevier; Elsevier Limited
• Subjects: Adolescent; Adult; Allergic asthma; Allergies; Allergy and Immunology; Asthma; Asthma - immunology; Asthma - physiopathology; Biological and medical sciences; CD4 Antigens - analysis; CD4+ T cells; Chronic obstructive pulmonary disease, asthma; Family medical history; Female; Forced Expiratory Volume; Forkhead Transcription Factors - analysis; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Homeostasis; Humans; Hypotheses; Immunopathology; induced sputum; late asthmatic responses; Lymphocytes; Male; Medical sciences; Middle Aged; Pneumology; regulatory T cells; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Sputum - immunology; T-Lymphocytes, Regulatory - immunology; Allergic asthma; Isolated early responder; late asthmatic responses; Treg; CD4 + T cells; FACS; DR; regulatory T cells; Late asthmatic response; Dual responder; Fluorescence-activated cell sorting; Forkhead box protein 3; EAR; IER; induced sputum; Regulatory T; Early asthmatic response; Foxp3; LAR; CD4+ T cells; Lung disease; Allergy; Immunopathology; Late; CD4 T lymphocyte; Respiratory disease; T cells; Asthma; CD4; Immunology; T-Lymphocyte; Bronchus disease; Early; Obstructive pulmonary disease; Regulatory cell; Comparative study; Induced sputum; CD4(+) T cells
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2013.08.025

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.