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致敏小鼠对屋尘螨和热带无爪螨的口服耐受诱导:针对免疫球蛋白E的天然自身抗体的出现

Oral tolerance induction to Dermatophagoides pteronyssinus and Blomia tropicalis in sensitized mice: occurrence of natural autoantibodies to immunoglobulin E.

作者信息

Sato M N, Oliveira C R, Futata E A, Victor J R, Maciel M, Fusaro A E, Carvalho A F, Duarte A J S

机构信息

Laboratory of Allergy and Clinical and Experimental Immunology, School of Medicine of São Paulo, São Paulo, Brazil.

出版信息

Clin Exp Allergy. 2002 Nov;32(11):1667-74. doi: 10.1046/j.1365-2222.2002.01429.x.

Abstract

BACKGROUND

The dust mites Dermatophagoides pteronyssinus (Dp) and Blomia tropicalis (Bt) are important sources of indoor allergens in tropical and subtropical countries. Murine models allow the analysis of the immune response and regulation of IgE production to Dp and Bt allergens. Oral tolerance induces unresponsiveness in naive animals, but its application in sensitized animals can provide useful information to improve allergy therapy.

OBJECTIVE

To study the profile of IgE and IgG subclasses antibody upon oral administration with Bt and Dp extract in previously sensitized mice. Further, the occurrence of autoantibodies IgG anti-IgE in the immunization and in the oral tolerance was investigated.

METHODS

A/Sn mice were immunized with Bt or Dp extract in alum, orally administrated with 0.25 mg of Bt or Dp extract or PBS at the 6th, 7th and 8th days after immunization and boosted twice with their respective allergens. To analyse the mice groups, specific IgE antibodies were measured by passive anaphylaxis reaction and specific IgG subclasses and anti-IgE IgG autoantibody by ELISA assay.

RESULTS

IgE levels were markedly increased in Bt-immunized mice compared with Dp-immunized mice. A distinct profile of the specific isotypes was verified in Bt-immunized mice with a preferential production of IgG3 and IgA antibodies, whereas Dp-immunized mice developed high titres of anti-Dp IgG1, IgG2a and IgG2b antibodies. The antigen feeding inhibited IgE response in both fed-mice groups but only Dp-fed mice presented decreased levels of IgG antibodies. Free anti-IgE IgG autoantibodies were detected mainly in the Dp-immunization and they correlated with the antibody isotypes found against the allergen.

CONCLUSIONS

This is the first time that the murine-type I hypersensitivity is employed to study Bt-immunization, showing a marked IgE production, associated with IgG response, which is at least in part driven by T-independent antigens. The oral tolerance protocol in previously sensitized animals was able to down-modulate IgE response and points out this route as a strategy for allergy therapy.

摘要

背景

尘螨屋尘螨(Dp)和热带螨(Bt)是热带和亚热带国家室内过敏原的重要来源。小鼠模型可用于分析对Dp和Bt过敏原的免疫反应以及IgE产生的调节。口服耐受可诱导未致敏动物产生无反应性,但其在致敏动物中的应用可为改善过敏治疗提供有用信息。

目的

研究在先前致敏的小鼠中口服Bt和Dp提取物后IgE和IgG亚类抗体的情况。此外,还研究了免疫和口服耐受过程中抗IgE IgG自身抗体的出现情况。

方法

用明矾中的Bt或Dp提取物免疫A/Sn小鼠,在免疫后第6、7和8天口服0.25 mg Bt或Dp提取物或PBS,并用各自的过敏原进行两次加强免疫。为分析小鼠组,通过被动过敏反应测量特异性IgE抗体,通过ELISA测定特异性IgG亚类和抗IgE IgG自身抗体。

结果

与Dp免疫小鼠相比,Bt免疫小鼠的IgE水平显著升高。在Bt免疫小鼠中证实了特异性同种型的独特情况,优先产生IgG3和IgA抗体而Dp免疫小鼠产生高滴度的抗Dp IgG1、IgG2a和IgG2b抗体。抗原喂养抑制了两个喂养小鼠组中的IgE反应,但只有Dp喂养的小鼠IgG抗体水平降低。游离抗IgE IgG自身抗体主要在Dp免疫中检测到,并与针对过敏原的抗体同种型相关。

结论

这是首次使用小鼠I型超敏反应来研究Bt免疫,显示出显著的IgE产生,并伴有IgG反应,这至少部分由非T细胞依赖性抗原驱动。先前致敏动物的口服耐受方案能够下调IgE反应,并指出该途径是一种过敏治疗策略。

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