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Lung CD25 CD4 regulatory T cells suppress type 2 immune responses but not bronchial hyperreactivity
Husein Hadeiba1, Richard M Locksley
1Department of Medicine, University of California, San Francisco, CA 94143, USA.
Abstract:
To study the effects of chronic Ag deposition in the airway mucosa on CD4(+) T cell priming and subsequent airway disease, transgenic mice were generated that expressed OVA under the control of the surfactant protein C promoter. CD4 T cells from these mice were tolerant to OVA but this was overcome among spleen CD4 T cells by crossing to OVA-specific DO11.10 TCR-transgenic mice. Lungs from the double-transgenic mice developed lymphocytic infiltrates and modest mucus cell hyperplasia. Infiltrating cells were unaffected by the absence of either Rag-1 or Stat6, although the latter deficiency led to the disappearance of mucus. In the lung of double-transgenic mice, a large number of Ag-specific CD4 T cells expressed CD25 and functioned as regulatory T cells. The CD25(+) CD4 T cells suppressed proliferation of CD25(-) CD4 T cells in vitro and inhibited type 2 immune responses induced by aerosolized Ags in vivo. Despite their ability to suppress allergic type 2 immunity in the airways, however, CD25(+) CD4 regulatory T cells had no effect on the development of bronchial hyperreactivity.
Insights
Chronic antigen deposition in airways induces regulatory T cells (Tregs) that suppress type 2 immunity but fail to prevent bronchial hyperreactivity in mice.
Area of Science:
- Immunology
- Respiratory Medicine
- Allergy Research
Background:
- Chronic antigen exposure in the airways can lead to immune dysregulation and disease.
- Regulatory T cells (Tregs) play a crucial role in maintaining immune tolerance and preventing excessive inflammation.
Purpose of the Study:
- To investigate the impact of chronic antigen deposition in the airway mucosa on CD4(+) T cell priming.
- To determine the role of regulatory T cells in the development of airway disease and bronchial hyperreactivity.
Main Methods:
- Generation of double-transgenic mice expressing ovalbumin (OVA) under the surfactant protein C promoter, crossed with OVA-specific TCR-transgenic mice.
- Analysis of immune cell infiltration, mucus production, and T cell populations (CD4(+), CD25(+)) in the lungs.
- In vitro suppression assays and in vivo assessment of immune responses and bronchial hyperreactivity.
Main Results:
- Double-transgenic mice developed lymphocytic infiltrates and mucus cell hyperplasia in the lungs.
- A significant population of antigen-specific CD4(+) T cells expressed CD25 and exhibited regulatory T cell function.
- CD25(+) CD4(+) regulatory T cells suppressed CD4(+) T cell proliferation and type 2 immune responses in vivo.
- Regulatory T cells did not affect the development of bronchial hyperreactivity despite suppressing allergic airway immunity.
Conclusions:
- Chronic antigen deposition in the airways promotes the development of functional regulatory T cells.
- Airway regulatory T cells can suppress type 2 allergic immune responses but are ineffective in preventing bronchial hyperreactivity.
- These findings highlight a dissociation between immune suppression and the resolution of airway hyperresponsiveness.