Adel-Patient K, Créminon Ch, Boquet D, Wal J M, Chatel J M
Laboratoire Inra d'Immuno-Allergie Alimentaire, Bât 136, CEA de Saclay, 91191 Gif-sur-Yvette, France.
Allerg Immunol (Paris). 2002 Mar;34(3):77-81.
The therapeutic routes for the treatment of allergy have as their objective to prevent or diminish the specific IgE responsible for the appearance of the allergic reaction. This allergic reaction survives in the genetically predisposed subject and results in a dis-equilibrium of the "Th1-Th2 balance" by increasing the Th2 response. This Th2 response induces the production of IgE against environmental antigens, which from that time on become allergens. In this context, use of gene immunisation seems to be very interesting. The immunisation consists of the injection of an expression vector of bacterial origin, containing the cDNA of a protein of interest. Different studies have shown that the injection of such a plasmid into mice initiates a specific immune response of Th1 (IgG2a) type, stopping all further response of the Th2 (IgG1 and IgE) type. This "non-allergic" response is due to the intrinsic properties of the bacterial ADN, notably the presence of sequences of immunostimulants, the adjuvant of the Th1 response. We have sought to show such a preventative effect in the case of a food protein, bovine beta-lactoglobulin (BLG), a major allergen of cow's milk. Firstly, we made a expression plasmid that contained the cDNA of BLG. Intramuscular administration of this plasmid to mice allowed expression of the BLG in the native form at the site of the injection. The primary response induced by this type of immunisation is characterised by a mixed IgG1/IgG2a response and an absence of anti-BLG IgE. In addition, pre-immunisation of the mice with a plasmid that contained the cDNA of BLG prevented all further sensitisation with the protein administered by the intra-peritoneal route in the presence of alum, an adjuvant of the Th2 response. It appeared further that the preventative effect is dependent on the latent time between gene and protein immunisation. Prevention of the anti-BLG IgE response seems to result in an active inhibition by the cytokines such as interferon-gamma and interleukin 10, rather than a reduction in the production of type Th2 cytokines. Use of efficacious non-pathogenic vectors, that may be administered by the digestive route, could envisage a specific protection in the case of severe food allergies.
治疗过敏的途径旨在预防或减少引发过敏反应的特异性免疫球蛋白E（IgE）。这种过敏反应存在于具有遗传易感性的个体中，并通过增强辅助性T细胞2（Th2）反应导致“Th1-Th2平衡”失衡。这种Th2反应会诱导针对环境抗原产生IgE，从那时起这些环境抗原就成为了过敏原。在这种情况下，基因免疫疗法似乎非常有意义。免疫过程包括注射一种细菌来源的表达载体，该载体包含感兴趣蛋白质的互补脱氧核糖核酸（cDNA）。不同的研究表明，将这种质粒注射到小鼠体内会引发Th1（IgG2a）型特异性免疫反应，从而阻止Th2（IgG1和IgE）型的所有后续反应。这种“非过敏”反应归因于细菌脱氧核糖核酸（DNA）的内在特性，尤其是免疫刺激序列的存在，即Th1反应的佐剂。我们试图在食物蛋白——牛β-乳球蛋白（BLG）（牛奶中的一种主要过敏原）的案例中证明这种预防效果。首先，我们构建了一个包含BLG cDNA的表达质粒。将该质粒肌肉注射到小鼠体内，使得BLG能在注射部位以天然形式表达。这种免疫方式引发的初次反应的特征是出现混合的IgG1/IgG2a反应，且不存在抗BLG IgE。此外，用包含BLG cDNA的质粒对小鼠进行预先免疫，可防止在存在Th2反应佐剂明矾的情况下，通过腹腔途径给予该蛋白质引发的所有进一步致敏。进一步研究发现，预防效果取决于基因免疫和蛋白质免疫之间的潜伏时间。抗BLG IgE反应的预防似乎是由细胞因子如干扰素-γ和白细胞介素10的主动抑制导致的，而不是Th2型细胞因子产生的减少。使用可通过消化道途径给药的有效非致病载体，有望在严重食物过敏的情况下实现特异性保护。
