Quantitative and functional impairment of pulmonary CD4+ CD25hi regulatory T cells in pediatric asthma

• Published in: Journal of allergy and clinical immunology 2007-05, Vol.119 (5), p.1258-1266
• Main Authors: Hartl, Dominik, MD, Koller, Barbara, MD, Mehlhorn, Alexander T., MD, Reinhardt, Dietrich, MD, Nicolai, Thomas, MD, Schendel, Dolores J., PhD, Griese, Matthias, MD, Krauss-Etschmann, Susanne, MD
• Format: Article
• Language: English
• Subjects: Adrenal Cortex Hormones - therapeutic use; Allergies; Allergy and Immunology; Anti-Asthmatic Agents - therapeutic use; Asthma; Asthma - drug therapy; Asthma - immunology; Autoimmune diseases; Biological and medical sciences; Bronchoalveolar Lavage Fluid - chemistry; Bronchoalveolar Lavage Fluid - cytology; Chemokines; Child; Chronic illnesses; Cytokines - biosynthesis; Flow Cytometry; Forkhead Transcription Factors - immunology; Forkhead Transcription Factors - metabolism; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Hospitals; Human subjects; Humans; Hypotheses; Immune system; Immunopathology; Interleukin-2 Receptor alpha Subunit - metabolism; Lung - immunology; Lung diseases; Lymphocytes; Medical sciences; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - analysis; Studies; T-Lymphocyte Subsets - immunology; T-Lymphocytes, Regulatory - immunology
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2007.02.023

Background Asthma is characterized by a TH 2 immune response. CD4+ CD25hi regulatory T cells (Tregs) have been proposed to prevent allergic diseases through suppression of TH 2 responses. Objective We sought to investigate the role of CD4+ CD25hi T cells in children with asthma. Methods CD4+ CD25hi Tregs and forkhead/winged-helix transcription factor FOXP3 mRNA levels were quantified in peripheral blood and bronchoalveolar lavage fluid (BALF) of 18 children with asthma, 10 children with chronic cough, and 13 control subjects without lung diseases. CD4+ CD25hi T cells were isolated from peripheral blood and BALF of asthmatic patients and control subjects, and their capacity to suppress proliferation and cytokine/chemokine production of autologous responder T cells was analyzed. Results CD4+ CD25hi T cells were decreased in BALF of asthmatic children compared with values in children with cough or control subjects. In children with asthma, inhaled corticosteroid treatment was associated with increased percentages of CD4+ CD25hi T cells in peripheral blood and BALF. Isolated BALF and peripheral blood CD4+ CD25hi T cells from nonasthmatic subjects suppressed proliferation and cytokine/chemokine production by CD4+ CD25− responder T cells. BALF CD4+ CD25hi T cells from asthmatic subjects failed to suppress proliferation and production of TH 2-associated cytokines and chemokines by CD4+ CD25− responder T cells, which was restored after use of inhaled corticosteroids. Conclusion These findings provide the first evidence that pulmonary CD4+ CD25hi Tregs are impaired in pediatric asthma. Clinical implications Pulmonary Tregs might represent a therapeutic target in pediatric asthma.