ANTI-IDIOTYPIC CONTROL OF NEURAL AND ALLERGIC DISEASES

实验性自身免疫性重症肌无力(EAMG) 鱼雷乙酰免疫C57BL/6小鼠产生 胆碱受体。我们实验室已经研制出抑制性T细胞 小鼠免疫后淋巴结细胞来源的细胞系和克隆 动物。目前的建议分为三个阶段。第一 其中两个与丰富辅助性和辅助性T细胞系有关 抑制活性并将这些株系杂交形成 永生化的T细胞杂交瘤。我们的方法将是诱导 通过包括抗原偶联在内的各种手段抑制T细胞 细胞，并用全淋巴球对动物进行预处理 辐射。来自动物的细胞，其中有抑制细胞 将通过平移和莲座化两种方法来丰富 在杂交之前。最后，T细胞将被杂交并 被选为抑制淋巴结细胞增殖的能力 免疫的淋巴细胞，并抑制抗体 体外产生和测量的迟发型超敏反应 耳朵肿胀和脚垫肿胀。产品的生产 辅助性T细胞杂交将被用于促进对 实验教学发展的潜力增强 小鼠品系中的自身免疫性重症肌无力。如果转让给 帮手杂交种在敏感品系中诱导疾病，然后 化学、药物或X射线对这类杂交物的衰减方法 都在考虑之中。 本提案的一个主要新主旨是研究 网络诱发的肌无力综合征。在这个综合征中 虚弱是由独特型的动物免疫引起的 由乙酰胆碱受体的配体产生的抗体。这 综合征在许多方面更接近人类的模型 那么疾病是在实验性自身免疫中产生的 鱼雷乙酰免疫动物后的肌无力 胆碱受体。将使用两种配体来研究该体系： 暹罗眼镜蛇神经毒素和抗AChR抗体。在这两个 本提案的部分内容我们使用网络是为了了解 免疫系统中的自然调节因素导致 临床肌无力的发展，从而希望 调整这些因素。 我们最近成功地给小鼠接种了疫苗 用32个氨基酸的寡肽制备EAMG 乙酰胆碱受体。该多肽现在将作为一种 抑制性细胞、辅助性细胞的诱导剂，以及作为耐受剂。

Experimental autoimmune myasthenia gravis (EAMG) has been produced in C57BL/6 mice by immunization with torpedo acetyl choline receptor. Our laboratory has developed suppressor T cell lines and clones derived from lymph node cells of immunized animals. The present proposal concerns three phases. The first two have to do with enriching T cell lines for both helper and suppressor activity and hybridizing these lines to form immortalized T cell hybridomas. Our method will be to induce suppressor T cells by a variety of means including antigen coupled cells, and by pretreating the animals with total lymphoid irradiation. Cells from animals in whom suppressor cells have been induced will be enriched by both panning and rosetting means prior to hybridization. Finally, T cells will be hybridized and selected for the capacity to suppress lymph node cell proliferation of immunized lymph node cells, and to suppress antibody production in vitro and delayed type hypersensitivity as measured both by ear swelling and footpad swelling. The production of helper T cell hybrids will be used to facilitate study of the potential augmentation of the development of experimental autoimmune myasthenia gravis in mouse strains. If transfer of helper hybrids induces the disease in susceptible strains, then means of attenuation of such hybrids with chemical, drug or X-ray are contemplated. A major new thrust of the present proposal is the study of network induced myasthenic syndrome. In this syndrome weakness is induced by immunization of animals with the idiotypic antibodies produced by ligands of the acetylcholine receptor. This syndrome is, in many respects, closer to the model of human disease then is that produced in experimental autoimmune myasthenia after immunizing animals with the torpedo acetyl choline receptor. Two ligands will be used to study this system: siamese cobra neurotoxin, and anti-AChR antibodies. In both the parts of this proposal our use of the network is to understand natural regulatory factors in the immune system leading to the development of clinical myasthenia and thereby hoping to modulate these factors. We have recently been successful in immunizing mice and producing EAMG with a 32 amino-acid oligopeptide of the acetylcholine receptor. This peptide will now be studied as an inducer of suppressor cells, helper cells, and as a toleragen.