Olsberg C A, Mikiten T M, Krolick K A
J Immunol. 1985 Nov;135(5):3062-7.
Purified acetylcholine receptor (AChR) covalently coupled to the catalytically toxic A chain of ricin has been used to selectively eliminate rat lymph node cells involved in in vitro anti-AChR antibody responses. The resulting inhibition was specific in view of the lack of such inhibition of anti-Keyhole limpet hemocyanin antibody responses. Furthermore, when fractionated B cell or T cell populations were treated with AChR-A chain, both populations were found to be sensitive to the specific cytotoxicity. However, T cell cytotoxicity required higher concentrations of the immunotoxin. Furthermore, when AChR-immune lymphocytes were treated with AChR-A chain in vitro, they became unable to mediate secondary adoptive transfer responses in vivo. The abrogation of the anti-AChR adoptive response correlated with the lack of muscle weakness characteristic of experimental autoimmune myasthenia gravis. Thus, it is possible, in principle, to eliminate clones of antigen-reactive lymphocytes with antigen-ricin A chain immunotoxins. This lets open the possibility of using such agents in immunotherapeutic approaches to autoimmune disease.
与蓖麻毒素具有催化毒性的A链共价偶联的纯化乙酰胆碱受体（AChR）已被用于选择性清除参与体外抗AChR抗体反应的大鼠淋巴结细胞。鉴于对抗钥孔血蓝蛋白抗体反应缺乏这种抑制作用，所产生的抑制作用具有特异性。此外，当用AChR-A链处理分离的B细胞或T细胞群体时，发现这两个群体对特异性细胞毒性均敏感。然而，T细胞细胞毒性需要更高浓度的免疫毒素。此外，当体外将AChR免疫淋巴细胞用AChR-A链处理时，它们在体内变得无法介导二次过继转移反应。抗AChR过继反应的消除与实验性自身免疫性重症肌无力缺乏肌肉无力特征相关。因此，原则上有可能用抗原-蓖麻毒素A链免疫毒素清除抗原反应性淋巴细胞克隆。这为在自身免疫性疾病的免疫治疗方法中使用此类药物开辟了可能性。
