Boudousquié C, Pellaton C, Barbier N, Spertini F
Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
Clin Exp Allergy. 2009 Sep;39(9):1415-26. doi: 10.1111/j.1365-2222.2009.03314.x. Epub 2009 Jul 16.
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.
To examine the role of Tregs in tolerance induction in a murine model of asthma.
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.
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.
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.
调节性T细胞（Tregs）是控制气道炎症发展的关键因素。然而，它们在已建立的过敏性哮喘中导致免疫耐受的机制中的作用尚不清楚。
研究Tregs在哮喘小鼠模型中诱导免疫耐受的作用。
用抗CD25 PC61单克隆抗体（mAb）清除或不清除卵清蛋白（OVA）致敏的哮喘小鼠的CD25(+) T细胞，然后在鼻内给予OVA治疗（INT），随后用OVA气雾剂激发。为了进一步评估CD4(+)CD25(+)和CD4(+)CD25(-) T细胞各自的调节活性，将这两个T细胞亚群从耐受或未耐受的动物转移到哮喘受体中。检测支气管肺泡灌洗液（BALF）、T细胞增殖和细胞因子分泌情况。
鼻内给予OVA导致肺匀浆中白细胞介素-10（IL-10）、转化生长因子-β（TGF-β）和白细胞介素-17水平升高，抑制嗜酸性粒细胞向BALF募集以及抗原特异性T细胞反应低下。肺中CD4(+)CD25(+)Foxp3(+) T细胞明显上调，并在体外和体内抑制OVA特异性T细胞反应。OVA INT前清除CD25(+)细胞严重阻碍了耐受诱导，表现为嗜酸性粒细胞大量募集到BALF中以及激发后对OVA的强烈T细胞反应。然而，与CD4(+)CD25(+) T细胞相反，CD4(+)CD25(-) T细胞的转移不仅抑制抗原特异性T细胞反应性，还显著减少嗜酸性粒细胞募集。与对照小鼠相比，来自OVA处理小鼠的CD4(+)CD25(-) T细胞中表达mTGF-β的比例明显更高。
CD4(+)CD25(+)和CD4(+)CD25(-) T细胞似乎对耐受诱导都至关重要。这两个亚群之间的关系及其调节活性机制有待进一步分析。
