Article: article from journal or magazin.
CD4+CD25+ T cell depletion impairs tolerance induction in a murine model of asthma.
Clinical and Experimental Allergy
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-beta 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-beta. 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.
Animals, Antibodies, Monoclonal/immunology, Antibodies, Monoclonal/pharmacology, Asthma/chemically induced, Asthma/immunology, Bronchoalveolar Lavage, Cytokines/biosynthesis, Cytokines/immunology, Disease Models, Animal, Eosinophils/immunology, Eosinophils/metabolism, Female, Gene Expression Regulation/drug effects, Gene Expression Regulation/immunology, Immune Tolerance, Lymphocyte Depletion, Mice, Mice, Inbred BALB C, RNA, Messenger/biosynthesis, RNA, Messenger/immunology, T-Lymphocytes, Regulatory/immunology, T-Lymphocytes, Regulatory/metabolism
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