Sehon A H
Department of Immunology, University of Manitoba, Winnipeg, Canada.
Int Arch Allergy Appl Immunol. 1991;94(1-4):11-20.
Some of the studies employing nonantigenic, nonallergenic and tolerogenic derivatives of antigens and allergens, synthesized by coupling onto them an optimal number (n) of molecules of monomethoxy-polyethylene glycol (mPEG), are briefly reviewed. Administration of antigen (mPEG)n conjugates into mice resulted in specific immunosuppression, which was mediated by antigen-specific suppressor T (Ts) cells and by suppressor factor(s) (TsF) produced by these cells. These Ts cells were cloned and shown to be Thy-1.2+, CD3+, CD4-, CD5-, CD8+, and expressed the alpha beta heterodimer of conventional T cell receptors (TCR). The TsF had the functional activity of Ts cells and possessed at least one epitope related to the alpha-chain of TCR. The results of clinical trials of mPEG conjugates of common allergens are briefly referred to; it is suggested that the time is opportune for the evaluation of the therapeutic efficacy of mPEG conjugates of pure allergens which can be synthesized on an industrial scale by recombinant DNA technology. Finally, possible applications of tolerogenic mPEG conjugates of xenogeneic monoclonal antibodies, immunotoxins and immunogenic recombinant lymphokines to the development of immunotherapeutic strategies in oncology, transplantation, autoimmunity and acquired immunodeficiency syndrome are discussed.
本文简要综述了一些研究，这些研究采用了通过将最佳数量（n）的单甲氧基聚乙二醇（mPEG）分子偶联到抗原和变应原上而合成的非抗原性、非变应原性和耐受性衍生物。将抗原（mPEG）n缀合物给予小鼠会导致特异性免疫抑制，这是由抗原特异性抑制性T（Ts）细胞以及这些细胞产生的抑制因子（TsF）介导的。这些Ts细胞被克隆出来，结果显示为Thy-1.2 +、CD3 +、CD4 -、CD5 -、CD8 +，并表达常规T细胞受体（TCR）的αβ异二聚体。TsF具有Ts细胞的功能活性，并拥有至少一个与TCRα链相关的表位。文中简要提及了常见变应原的mPEG缀合物的临床试验结果；有人认为，现在是评估可通过重组DNA技术进行工业规模合成的纯变应原的mPEG缀合物治疗效果的适当时机。最后，还讨论了异种单克隆抗体、免疫毒素和免疫原性重组淋巴因子的耐受性mPEG缀合物在肿瘤学、移植、自身免疫和获得性免疫缺陷综合征免疫治疗策略开发中的可能应用。
