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

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Background

Asthma is characterized by a TH2 immune response. CD4+CD25hi regulatory T cells (Tregs) have been proposed to prevent allergic diseases through suppression of TH2 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 TH2-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.

Section snippets

Patients

Eighteen children with asthma, 10 children with chronic cough, and 13 control children without lung diseases were characterized18, 19 and included in this study (see Table E1 in the Online Repository at www.jacionline.org). For a detailed patient characterization, see the Methods section in the Online Repository at www.jacionline.org.

Bronchoalveolar lavage

Bronchoscopy was performed by using a flexible bronchoscope with an outer diameter of 3.5 mm in children less than 10 years of age and a 4.9-mm diameter in older

Decreased CD4+CD25hi T cells in BALF of children with asthma

Taking all groups together, peripheral blood T cells included a median of 5% total CD4+CD25hi+low T cells (range, 4% to 8%) and a median of 1.9% CD4+CD25hi T cells (range, 1.4% to 2.4%), whereas BALF T cells contained a median of 12% CD4+CD25hi+low T cells (range, 2% to 19%) and a median of 6.5% CD4+CD25hi T cells (range, 1% to 10.2%). CD4+CD25hi T cells in peripheral blood and BALF were CD45RO+ (95% and 90%, respectively) and did not express the early activation marker CD69. In peripheral

Discussion

The present work demonstrates, for the first time in human subjects, that CD4+CD25hi T cells are enriched in the bronchoalveolar space compared with in peripheral blood and are fully capable of suppressing T-cell responses. However, in asthmatic children pulmonary CD4+CD25hi T cells are decreased in number and fail to suppress TH2 responses. Inhaled corticosteroid treatment in asthmatic subjects increases pulmonary CD4+CD25hi T cells and restores their suppressive function.

With few exceptions,23

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  • Cited by (0)

    Supported by grants from the Else-Kröner-Fresenius Stiftung and the Friedrich-Baur-Stiftung, a grant of the University and Science Program of the Ludwig-Maximilians-University (HWP), and by the Clinical Cooperation Groups “Pediatric Immune Regulation” and “Immune Monitoring.” Dominik Hartl, MD, is supported by the Society for Pediatric Pneumology (GPP).

    Disclosure of potential conflict of interest: The authors have declared that they have no conflict of interest.

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