CD4+CD25-mTGFbeta+ T cells induced by nasal application of ovalbumin transfer tolerance in a therapeutic model of asthma.

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Serval ID
serval:BIB_1774B9E1DDBE
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
CD4+CD25-mTGFbeta+ T cells induced by nasal application of ovalbumin transfer tolerance in a therapeutic model of asthma.
Journal
International Immunology
Author(s)
Pellaton-Longaretti C., Boudousquié C., Barbier N., Barbey C., Argiroffo C.B., Donati Y., Sauty A., Spertini F.
ISSN
1460-2377[electronic], 0953-8178[linking]
Publication state
Published
Issued date
2011
Volume
23
Number
1
Pages
17-27
Language
english
Abstract
Background: Intranasal administration of high amount of allergen was shown to induce tolerance and to reverse the allergic phenotype. However, mechanisms of tolerance induction via the mucosal route are still unclear. Objectives: To characterize the therapeutic effects of intranasal application of ovalbumin (OVA) in a mouse model of bronchial inflammation as well as the cellular and molecular mechanisms leading to protection upon re-exposure to allergen. Methods: After induction of bronchial inflammation, mice were treated intranasally with OVA and re-exposed to OVA aerosols 10 days later. Bronchoalveolar lavage fluid (BALF), T cell proliferation and cytokine secretion were examined. The respective role of CD4(+)CD25(+) and CD4(+)CD25(-) T cells in the induction of tolerance was analysed. Results: Intranasal treatment with OVA drastically reduced inflammatory cell recruitment into BALF and bronchial hyperresponsiveness upon re-exposure to allergen. Both OVA- specific-proliferation of T cells, T(h)1 and T(h)2 cytokine production from lung and bronchial lymph nodes were inhibited. Transfer of CD4(+)CD25(-) T cells, which strongly expressed membrane-bound transforming growth factor beta (mTGF beta), from tolerized mice protected asthmatic recipient mice from subsequent aerosol challenges. The presence of CD4(+)CD25(+)(Foxp3(+)) T cells during the process of tolerization was indispensable to CD4(+)CD25(-) T cells to acquire regulatory properties. Whereas the presence of IL-10 appeared dispensable in this model, the suppression of CD4(+)CD25(-)mTGF beta(+) T cells in transfer experiments significantly impaired the down-regulation of airways inflammation. Conclusion: Nasal application of OVA in established asthma led to the induction of CD4(+)CD25(-)mTGF beta(+) T cells with regulatory properties, able to confer protection upon allergen re-exposure.
Pubmed
Web of science
Open Access
Yes
Create date
28/01/2011 15:52
Last modification date
25/09/2019 6:08
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