Sensitizing and Th2 Adjuvant Activity of Cysteine Protease Allergens
Sensitizing and Th2 Adjuvant Activity of Cysteine Protease Allergens
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DOI：
10.1159/000334280
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发表时间：
2012-01-01
影响因子：
2.8
通讯作者：
Thomas，Wayne R.
中科院分区：
文献类型：
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作者：
Cunningham，Paula T.;Elliot，Claire E.;Thomas，Wayne R.
背景增强免疫应答的固有特性可能增加某些过敏原诱导过敏性致敏的倾向。直接的佐剂效应或对过敏原的免疫应答的增加则可以增加对旁观者抗原的过敏应答。在这里，我们报告一个模型，不使用Th 2-偏移佐剂，但实现敏化单独通过鼻mucosa.MethodsAnimals通过鼻粘膜与酶活性，非活性或非活化的半胱氨酸蛋白酶致敏。在两个致敏阶段之后，用更高剂量的过敏原攻击小鼠。对于旁观者致敏，小鼠在致敏时接受与半胱氨酸蛋白酶联合的重组Der p 2，并用rDer p 2单独攻击。致敏测定通过测量过敏原特异性抗体反应和细胞因子和细胞浸润到肺后challenge.ResultsSensitization为Th 2型肺超敏反应的半胱氨酸蛋白酶和旁观者抗原很容易实现，都依赖于蛋白水解活性的过敏原。对于作为半胱氨酸蛋白酶的低IgE应答者的小鼠，证明了旁观者佐剂活性，显示出独立于对增强性半胱氨酸蛋白酶的免疫应答的应答。气道高反应性诱导的敏感NOD品系的小鼠，和小鼠进行长期管理的木瓜蛋白酶保持产生肺超敏反应和Th 2型respons.ConclusionsThese实验表明，在低剂量的半胱氨酸蛋白酶活性可以是一种佐剂的情况下，另一种佐剂的呼吸Th 2反应为自己和旁观者抗原。
BackgroundInnate properties that enhance immune responses might increase the propensity of certain allergens to induce allergic sensitization. Either a direct adjuvant effect or the increased immune response to the allergen could then increase allergic responses to bystander antigens. Here, we report on a model that does not use Th2-skewing adjuvants and yet achieves sensitization solely via the nasal mucosa.MethodsAnimals were sensitized with either enzymatically active, inactive or non-activated cysteine proteases via the nasal mucosa. Following two sensitization phases, mice were challenged with a higher dose of allergen. For bystander sensitization, mice received recombinant Der p 2 at sensitization in conjunction with the cysteine protease and were challenged with rDer p 2 alone. Sensitization was determined by measuring allergen-specific antibody responses and cytokine and cellular infiltrates into the lungs following challenge.ResultsSensitization for Th2-type lung hypersensitivity for both the cysteine protease and bystander antigens was readily achieved and both were dependent on the proteolytic activity of the allergen. Bystander adjuvant activity was demonstrated for mice that were low IgE responders to the cysteine protease, showing a response independent from the immune response to the enhancing cysteine protease. Airway hyperreactivity was induced in the susceptible NOD strain of mouse, and mice subjected to prolonged administration of papain maintained the ability to produce lung hypersensitivity and Th2-type responses.ConclusionsThese experiments demonstrate that cysteine protease activity at low doses can be an adjuvant for respiratory Th2 responses for themselves and bystander antigens in the absence of another adjuvant.