aUniversité Paris Descartes, France bINSERM, Unité 1013, Paris, France *Sylvaine You and Lucienne Chatenoud contribute equally to the writing of this article.
Curr Opin Organ Transplant. 2010 Dec;15(6):720-4. doi: 10.1097/MOT.0b013e3283402bd8.
The continuing problem of late graft loss and immunosuppressive drug toxicity forces us to explore new treatments for the induction of transplant tolerance. Monoclonal antibodies targeting molecules implicated in lymphocyte activation, in particular CD3/TCR, constitute a promising strategy.
Promising results were obtained from the use of antibodies targeting CD3/TCR, coreceptors or costimulatory pathways as tolerance-promoting tools in experimental transplantation. These antibodies do not uniformly depress the immune system but act in an antigen-specific manner by preferentially targeting effector T cells while preserving regulatory T cells. However, translation to the clinic proved to be more difficult than expected. New generation CD3 antibodies, currently used in phase II/III trials in autoimmunity, constitute a promising approach as, beside their immunosuppressive effect, they also express potent tolerogenic capacities. Importantly, CD3 therapy is effective especially when applied in primed hosts, highlighting the importance of the therapeutic window for tolerance induction.
Further investigations are required for adapting to the clinic monoclonal antibodies as substitutes for current immunosuppression. Our aim is to show that development of new therapeutic strategies/molecules may come from transversal-type research, in particular from experience in autoimmunity, as immune responses leading to autoimmunity and graft rejection involve similar pathways.
晚期移植物失功和免疫抑制剂毒性的持续问题迫使我们探索新的治疗方法来诱导移植耐受。靶向淋巴细胞激活相关分子（特别是 CD3/TCR）的单克隆抗体是一种很有前途的策略。
在实验性移植中，使用靶向 CD3/TCR、共受体或共刺激途径的抗体作为诱导耐受的工具，取得了令人鼓舞的结果。这些抗体不会普遍抑制免疫系统，而是通过优先靶向效应 T 细胞而保留调节性 T 细胞，以抗原特异性方式发挥作用。然而，向临床的转化比预期的更为困难。目前在自身免疫性疾病的 II/III 期临床试验中使用的新一代 CD3 抗体作为一种很有前途的方法，因为除了具有免疫抑制作用外，它们还具有很强的耐受能力。重要的是，CD3 治疗在预先致敏的宿主中特别有效，这突出了诱导耐受的治疗窗口的重要性。
需要进一步研究将单克隆抗体适应于临床，作为当前免疫抑制的替代物。我们的目标是表明，开发新的治疗策略/分子可能来自于横向研究，特别是来自于自身免疫的经验，因为导致自身免疫和移植物排斥的免疫反应涉及相似的途径。
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