CD4+CD25+ T cell depletion impairs tolerance induction in a murine model of asthma
CD4+CD25+ T cell depletion impairs tolerance induction in a murine model of asthma
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DOI：
10.1111/j.1365-2222.2009.03314.x
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发表时间：
2009-09-01
影响因子：
6.1
通讯作者：
Spertini, F.
中科院分区：
文献类型：
--
作者：
Boudousquie, C.;Pellaton, C.;Spertini, F.
背景调节性T细胞（Regulatory T cells，Tcells）是控制气道炎症发展的关键细胞.目的研究Tcl 4在哮喘小鼠模型中诱导耐受的作用。方法卵清蛋白（OVA）致敏哮喘小鼠，在用OVA鼻内给药（INT）前，用抗CD 25 PC 61单克隆抗体（mAb）去除或不去除CD 25（+）T细胞，然后用OVA气雾剂激发。为了进一步评价CD 4（+）CD 25（+）和CD 4（+）CD 25（-）T细胞各自的调节活性，将两种T细胞亚群从耐受化或非耐受化动物转移至哮喘受体。支气管肺泡灌洗液（BALF），T细胞增殖和细胞因子分泌进行了检查。ResultsIntranasal处理与OVA导致肺匀浆中的IL-10，TGF-β和IL-17的水平增加，抑制嗜酸性粒细胞招募到BALF和抗原特异性T细胞低反应。CD 4（+）CD 25（+）Foxp 3（+）T细胞在肺中显著上调，并在体外和体内抑制OVA特异性T细胞应答。OVA INT前CD 25（+）细胞的耗竭严重阻碍了耐受性诱导，如嗜酸性粒细胞向BALF中的强烈募集和激发后对OVA的强烈T细胞应答所示。然而，与CD 4（+）CD 25（+）T细胞相比，CD 4（+）CD 25（-）T细胞的转移不仅抑制抗原特异性T细胞反应性，而且显著减少嗜酸性粒细胞募集。与对照组相比，OVA处理组小鼠的CD 4（+）CD 25（-）T细胞表达mTGF-β的比例明显增高。结论CD 4（+）CD 25（+）和CD 4（+）CD 25（-）T细胞在免疫耐受诱导中均起重要作用。这两个子集之间的关系及其调节活性的机制将进一步分析。
P>BackgroundRegulatory 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.ObjectiveTo examine the role of Tregs in tolerance induction in a murine model of asthma.MethodsOvalbumin (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.ResultsIntranasal 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.ConclusionBoth 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.