CD137 deficiency does not affect development of airway inflammation or respiratory tolerance induction in murine models
CD137 deficiency does not affect development of airway inflammation or respiratory tolerance induction in murine models
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DOI：
10.1111/j.1365-2249.2012.04572.x
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发表时间：
2012-06-01
影响因子：
4.6
通讯作者：
Hansen, G.
中科院分区：
文献类型：
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作者：
Behrendt, A-K.;Meyer-Bahlburg, A.;Hansen, G.
共刺激分子 CD137 (4-1BB) 在哮喘的发生和持续过程中发挥着至关重要的作用，其特征是嗜酸性气道炎症、粘液分泌过多、气道高反应性、辅助性 T 2 型 (Th2) 细胞因子产生和血清免疫球蛋白 (Ig)E 水平增加。我们之前已经证明，应用激动性 CD137 单克隆抗体 (mAb) 可以预防甚至逆转已经确定的哮喘表型。在当前的研究中，我们研究了 CD137/CD137L 通路的缺陷是否会影响过敏性气道炎症的发展或呼吸耐受的相反免疫反应。 CD137-/- 和野生型 (WT) 小鼠被模型过敏原卵清蛋白 (OVA) 致敏和攻击，并分析过敏性疾病参数的存在（过敏方案）。在将动物转移到过敏方案之前，通过粘膜应用 OVA 来耐受一些动物，以分析 CD137 缺失对耐受诱导（耐受方案）的影响。 CD137-/- 和 WT 小鼠中嗜酸性粒细胞性气道炎症、粘液分泌过多、Th2 细胞因子产生和过敏原特异性血清 IgE 水平升高相同。诱导耐受对两种小鼠品系的过敏表型产生具有相当的保护作用。此外，在 CD4+、CD8+ 和叉头盒蛋白 3 (FoxP3+) 调节性 T 细胞中未发现显着差异，这支持了 CD137-/- 小鼠与 WT 小鼠相比表现出相同的 Th2 介导的免疫反应的结论。总的来说，CD137-/- 小鼠和 WT 小鼠在 Th2 介导的过敏性气道炎症和呼吸耐受的小鼠模型中表现出相同的表型。
The co-stimulatory molecule CD137 (4-1BB) plays a crucial role in the development and persistence of asthma, characterized by eosinophilic airway inflammation, mucus hypersecretion, airway hyperreactivity, increased T helper type 2 (Th2) cytokine production and serum immunoglobulin (Ig)E levels. We have shown previously that application of an agonistic CD137 monoclonal antibody (mAb) prevented and even reversed an already established asthma phenotype. In the current study we investigated whether deficiency of the CD137/CD137L pathway affects the development of allergic airway inflammation or the opposite immune reaction of respiratory tolerance. CD137-/- and wild-type (WT) mice were sensitized and challenged with the model allergen ovalbumin (OVA) and analysed for the presence of allergic disease parameters (allergy protocol). Some animals were tolerized by mucosal application of OVA prior to transferring the animals to the allergy protocol to analyse the effect of CD137 loss on tolerance induction (tolerance protocol). Eosinophilic airway inflammation, mucus hypersecretion, Th2 cytokine production and elevated allergen-specific serum IgE levels were increased equally in CD137-/- and WT mice. Induction of tolerance resulted in comparable protection from the development of an allergic phenotype in both mouse strains. In addition, no significant differences could be identified in CD4+, CD8+ and forkhead box protein 3 (FoxP3+) regulatory T cells, supporting the conclusion that CD137-/- mice show equal Th2-mediated immune responses compared to WT mice. Taken together, CD137-/- mice and WT mice develop the same phenotype in a murine model of Th2-mediated allergic airway inflammation and respiratory tolerance.