Snanoudj Renaud, Frangié Carlos, Deroure Benjamin, François Hélène, Créput Caroline, Beaudreuil Séverine, Dürrbach Antoine, Charpentier Bernard
Service de Néphrologie et Transplantation Rénale, Hôpital du Kremlin Bicêtre, Assistance Publique Hôpitaux de Paris; Le Kremlin-Bicêtre; France.
Biologics. 2007 Sep;1(3):203-13.
The development of immunosuppressive drugs has in recent years been focused on prevention of acute rejection. This has led to an increase in one-year allograft survival. However, these drugs have non-immune effects which contribute to the high incidence of late graft loss, as a consequence of chronic allograft nephropathy, and the death of patients. As an immune-specific alternative to conventional immunosuppressants, new biotechnology tools have been developed; they target the costimulation signal of T-cell activation, particularly by the "classical" B7/CD28 and CD40/CD40L pathways. Here, we review the limitations of current immunosuppressive protocols, the benefits of classical B7/CD28 costimulation blockade, and the first large-scale clinical application of this strategy to human transplantation with belatacept. We will also consider novel costimulatory molecules of the B7/CD28 and TNF/TNF-R families, which appear to be important for the functions of memory and effector T-cells.
近年来，免疫抑制药物的研发主要集中在预防急性排斥反应上。这使得同种异体移植物的一年生存率有所提高。然而，这些药物具有非免疫效应，会导致慢性同种异体移植肾病造成的晚期移植物丢失发生率较高，以及患者死亡。作为传统免疫抑制剂的免疫特异性替代物，人们开发了新的生物技术工具；它们靶向T细胞活化的共刺激信号，特别是通过“经典的”B7/CD28和CD40/CD40L途径。在此，我们综述了当前免疫抑制方案的局限性、经典B7/CD28共刺激阻断的益处，以及该策略在人类移植中使用贝拉西普的首次大规模临床应用。我们还将考虑B7/CD28和TNF/TNF-R家族的新型共刺激分子，它们似乎对记忆和效应T细胞的功能很重要。
