Wiedermann U, Jahn-Schmid B, Lindblad M, Rask C, Holmgren J, Kraft D, Ebner C
Division of Immunopathology, Institute of General and Experimental Pathology, University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.
Int Immunol. 1999 Oct;11(10):1717-24. doi: 10.1093/intimm/11.10.1717.
Recent reports have demonstrated that feeding small amounts of antigen conjugated to the B subunit of cholera toxin (CTB) suppress immune responses in experimental models of certain T(h)1-based autoimmune diseases. We have established a model of aerosol sensitization leading to T(h)2-mediated allergic immune responses in BALB/c mice. In the present study two different antigens, the dietary antigen ovalbumin (OVA) and the inhalant allergen Bet v 1 (the major birch pollen allergen), chemically coupled to recombinant CTB were tested for their potential to influence T(h)2-like immune responses. Intranasal administration of OVA-CTB prior to sensitization with OVA led to a significant decrease of antigen-specific IgE antibody levels, but a marked increase of OVA-specific IgG2a antibodies as compared to non-pretreated, sensitized animals. Antigen-specific lympho-proliferative responses in vitro were reduced by 65% in the pretreated group; IL-5 and IL-4 production were decreased in responder cells of lungs and spleens of nasally pretreated mice. In contrast, mucosal administration of rBet v 1-CTB conjugates prior to sensitization led to an up-regulation of allergen-specific IgE, IgG1 and IgG2a, increased in vitro lympho-proliferative responses as well as augmented production of IL-5, IL-4, IL-10 and IFN-gamma. Intranasal administration prior to sensitization of unconjugated allergens showed also contrasting effects: OVA could not significantly influence antigen-specific antibody or cytokine production, whereas intranasal pretreatment with unconjugated Bet v 1 suppressed allergen-specific immune responses in vivo and in vitro. These results demonstrated that the two antigens-in conjugated as in unconjugated form-had different effects on the T(h)2 immune responses. We therefore conclude that the tolerogenic or immunogenic properties of CTB-and probably also other antigen-delivery systems-strongly depend on the nature of the coupled antigen-allergen.
最近的报告表明，在某些基于Th1的自身免疫性疾病的实验模型中，喂食少量与霍乱毒素B亚基（CTB）偶联的抗原可抑制免疫反应。我们建立了一种气溶胶致敏模型，可在BALB/c小鼠中引发Th2介导的过敏性免疫反应。在本研究中，测试了两种不同的抗原，即与重组CTB化学偶联的饮食抗原卵清蛋白（OVA）和吸入性变应原Bet v 1（主要桦树花粉变应原）影响Th2样免疫反应的潜力。在用OVA致敏之前鼻内给予OVA-CTB，与未预处理的致敏动物相比，抗原特异性IgE抗体水平显著降低，但OVA特异性IgG2a抗体显著增加。预处理组体外抗原特异性淋巴细胞增殖反应降低了65%；鼻内预处理小鼠的肺和脾反应细胞中IL-5和IL-4的产生减少。相反，在致敏之前黏膜给予rBet v 1-CTB偶联物导致变应原特异性IgE、IgG1和IgG2a上调，体外淋巴细胞增殖反应增加，以及IL-5、IL-4、IL-10和IFN-γ的产生增加。在致敏之前鼻内给予未偶联的变应原也显示出相反的效果：OVA不能显著影响抗原特异性抗体或细胞因子的产生，而用未偶联的Bet v 1鼻内预处理可在体内和体外抑制变应原特异性免疫反应。这些结果表明，两种抗原——偶联形式和未偶联形式——对Th2免疫反应有不同的影响。因此，我们得出结论，CTB以及可能还有其他抗原递送系统的致耐受性或免疫原性特性在很大程度上取决于偶联抗原——变应原的性质。
