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CD4+CD25+ T cell depletion impairs tolerance induction in a murine model of asthma

Authors


Correspondence:
François Spertini, Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois, BH-19, Rue du Bugnon, 1011 Lausanne, Switzerland.
E-mail: francois.spertini@chuv.ch

Summary

Background Regulatory T cells (Tregs) are key players in controlling the development of airway inflammation. However, their role in the mechanisms leading to tolerance in established allergic asthma is unclear.

Objective To examine the role of Tregs in tolerance induction in a murine model of asthma.

Methods Ovalbumin (OVA) sensitized asthmatic mice were depleted or not of CD25+ T cells by anti-CD25 PC61 monoclonal antibody (mAb) before intranasal treatment (INT) with OVA, then challenged with OVA aerosol. To further evaluate the respective regulatory activity of CD4+CD25+ and CD4+CD25 T cells, both T cell subsets were transferred from tolerized or non-tolerized animals to asthmatic recipients. Bronchoalveolar lavage fluid (BALF), T cell proliferation and cytokine secretion were examined.

Results Intranasal treatment with OVA led to increased levels of IL-10, TGF-β and IL-17 in lung homogenates, inhibition of eosinophil recruitment into the BALF and antigen specific T cell hyporesponsiveness. CD4+CD25+Foxp3+ T cells were markedly upregulated in lungs and suppressed in vitro and in vivo OVA-specific T cell responses. Depletion of CD25+ cells before OVA INT severely hampered tolerance induction as indicated by a strong recruitment of eosinophils into BALF and a vigorous T cell response to OVA upon challenge. However, the transfer of CD4+CD25 T cells not only suppressed antigen specific T cell responsiveness but also significantly reduced eosinophil recruitment as opposed to CD4+CD25+ T cells. As compared with control mice, a significantly higher proportion of CD4+CD25 T cells from OVA treated mice expressed mTGF-β.

Conclusion Both CD4+CD25+ and CD4+CD25 T cells appear to be essential to tolerance induction. The relationship between both subsets and the mechanisms of their regulatory activity will have to be further analyzed.

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