ANTI-IDIOTYPIC CONTROL OF NEURAL AND ALLERGIC DISEASES

实验性自身免疫性重症肌无力（EAMG）已被 在C57 BL/6小鼠中通过用乙酰鱼雷免疫产生 胆碱受体 我们的实验室已经开发出抑制性T细胞 来源于免疫小鼠淋巴结细胞的细胞系和克隆 动物 本建议涉及三个阶段。 第一 两个与富集T细胞系的辅助细胞和 抑制子活性，并将这些品系杂交以形成 永生化T细胞杂交瘤。 我们的方法是 抑制性T细胞通过多种手段，包括抗原偶联 细胞，并用总淋巴细胞预处理动物， 辐照 来自动物的细胞，其中抑制细胞具有 将通过淘洗和玫瑰花结两种方式来丰富 在杂交之前。 最后，T细胞将被杂交， 选择抑制淋巴结细胞增殖的能力 免疫的淋巴结细胞，并抑制抗体 体外生产和迟发型超敏反应， 耳朵肿胀和脚垫肿胀。 生产 辅助性T细胞杂交将用于促进研究 实验发展的潜在增强 自身免疫性重症肌无力小鼠品系。 如果转让 辅助杂种在易感菌株中诱导疾病， 用化学品、药物或X射线减弱这种混合物的方法 都在考虑之列。 本建议的一个新的主要重点是研究 网络诱发的肌无力综合征 在这种综合症中 虚弱是通过用独特型 乙酰胆碱受体配体产生的抗体。 这 综合征在许多方面更接近人类的模型， 那么疾病就是实验性自身免疫性疾病 乙酰鱼雷免疫动物后的肌无力 胆碱受体 将使用两种配体来研究该系统： 暹罗眼镜蛇神经毒素和抗乙酰胆碱受体抗体。 两者中 我们使用网络的部分建议是为了了解 免疫系统中的天然调节因子， 临床肌无力的发展，从而希望 调整这些因素。 我们最近成功地免疫了老鼠， 用本发明的32个氨基酸的寡肽生产EAMG， 乙酰胆碱受体 这种肽现在将作为一种 抑制细胞、辅助细胞的诱导剂，以及作为耐受原。

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.