Comoy E E, Pestel J, Duez C, Stewart G A, Vendeville C, Fournier C, Finkelman F, Capron A, Thyphronitis G
INSERM U167 Institut Pasteur de Lille, France.
J Immunol. 1998 Mar 1;160(5):2456-62.
A common property of allergens is their potential to generate type 2 cytokine responses. To understand the mechanisms involved in this phenomenon, we have evaluated the polarizing potential of a major allergen, Dermatophagoides pteronyssinus 1 (Der p 1), in an heterologous immunization system using the glutathione S-transferase of the parasite Schistosoma mansoni (Sm28-GST) as immunogen. In previous studies, we showed that immunization with the Sm28-GST emulsified in CFA induced a nonpolarized immune response. In contrast, when alum was used as adjuvant, a type 2 immune response was induced against Sm28-GST. Using this experimental model, we examined whether the administration of Der p 1 together with Sm28-GST influenced the nonpolarized and/or the Th2 profiles induced by the CFA or the alum immunization, respectively. Our results showed that the introduction of Der p 1 in the CFA immunization protocol was associated with diminished anti-Sm28-GST IgG2a Ab titers, reduced IFN-gamma mRNA expression, and frequency of IFN-gamma-producing cells. In contrast, the introduction of Der p 1 in the alum protocol did not affect IL-4 or Ig isotype responses. The effect of Der p 1 was specific, since coimmunization with tetanus toxin fragment C did not affect the profile of the response against Sm28-GST. Furthermore, inactivation of Der p 1 reduced its ability to modify the immune response profile, suggesting that its protease activity played an important role in deviating the immune response. Our results suggest that the Der p 1 has the ability to modify the profile of an immune response by modulating the balance between the polarizing cytokines IL-4 and IFN-gamma.
变应原的一个共同特性是它们具有产生2型细胞因子反应的潜力。为了了解这一现象所涉及的机制,我们在一个异源免疫体系中评估了一种主要变应原——屋尘螨1(Der p 1)的极化潜力,该体系使用曼氏血吸虫的谷胱甘肽S-转移酶(Sm28-GST)作为免疫原。在先前的研究中,我们表明用弗氏完全佐剂(CFA)乳化的Sm28-GST免疫会诱导一种非极化的免疫反应。相反,当使用明矾作为佐剂时,会诱导针对Sm28-GST的2型免疫反应。利用这个实验模型,我们分别研究了Der p 1与Sm28-GST共同给药是否会影响由CFA或明矾免疫诱导的非极化和/或Th2型反应。我们的结果表明,在CFA免疫方案中引入Der p 1与抗Sm28-GST IgG2a抗体滴度降低、IFN-γ mRNA表达减少以及产生IFN-γ的细胞频率降低有关。相反,在明矾方案中引入Der p 1并不影响IL-4或Ig同种型反应。Der p 1的作用具有特异性,因为与破伤风毒素片段C共同免疫不会影响针对Sm28-GST的反应类型。此外,Der p 1的失活降低了其改变免疫反应类型的能力,这表明其蛋白酶活性在偏离免疫反应中起重要作用。我们的结果表明,Der p 1有能力通过调节极化细胞因子IL-4和IFN-γ之间的平衡来改变免疫反应的类型。