Chatenoud L, Bach J F
Unité INSERM 25, CNRS LA 122, Hôpital Necker, Paris.
Nephrologie. 1987;8(3):95-8.
The OKT3 monoclonal antibody, that is specific for all mature human T lymphocytes represents a potent immunosuppressant when injected in vivo. The OKT3 antibody has been administered to more than 500 renal allograft recipients either to treat or prevent acute rejection episodes. OKT3 exerts its immunosuppressive effect by inducing rapid and important T cell depletion following the first injection. Then, OKT3 mediates the antigenic modulation of its T cell target antigen a phenomenon that is also related to the immunosuppressive effect exerted by the monoclonal antibody. The principal side effect observed following OKT3 administration, particularly if the antibody is injected alone, is the xenosensitisation against the foreign protein. Essentially, two sorts of anti-OKT3 antibodies are produced that respectively recognize the isotypic and the idiotypic determinants of the antibody molecule. The different strategies that may be envisaged to overcome this important side effect, that may totally neutralize the therapeutic effectiveness of OKT3 are discussed in detail.
OKT3单克隆抗体对所有成熟的人类T淋巴细胞具有特异性,在体内注射时是一种强效免疫抑制剂。OKT3抗体已应用于500多名肾移植受者,用于治疗或预防急性排斥反应。OKT3通过在首次注射后诱导快速且显著的T细胞耗竭发挥其免疫抑制作用。然后,OKT3介导其T细胞靶抗原的抗原调制,这一现象也与单克隆抗体发挥的免疫抑制作用有关。OKT3给药后观察到的主要副作用,特别是单独注射抗体时,是对外源蛋白的异种致敏。基本上,会产生两种抗OKT3抗体,它们分别识别抗体分子的同种型和独特型决定簇。文中详细讨论了为克服这一可能完全抵消OKT3治疗效果的重要副作用而可能设想的不同策略。