Rifle Gérard, Mousson Christiane
Department of Nephrology-Intensive Care-Transplantation, Hôpital du Bocage, 2 boulevard de Lattre de Tassigny, 21034 Dijon, France.
Transplantation. 2003 May 15;75(9 Suppl):3S-7S. doi: 10.1097/01.TP.0000067943.90241.73.
Infusion of donor-derived cells can improve organ allograft survival in animal models. Under certain conditions, it can even induce tolerance (i.e., unlimited organ survival without any maintenance immunosuppressive therapy). Use of nonmyeloablative regimens allows engraftment of donor-derived bone marrow cells, induction of mixed chimerism, and tolerance in rodents. High doses of bone marrow cells together with anti-T-cell antibodies can even result in mixed chimerism without cytoablative host conditioning. Cultured donor-derived CD34+ cells or donor-derived immature (or even mature) dendritic cells associated with monoclonal antibodies directed against co-stimulatory molecules might also induce tolerance. Among the numerous experimental protocols leading to tolerance of solid organs in animal models, how can we find our bearings in human transplantation? Numerous problems have yet to be solved: the type and amount of donor-derived cells (including stromal cells) to be used, the timing for infusion of donor cells in keeping with organ transplantation, the route of infusion (should it be intravenous, into the portal vein?), and the conditioning regimen. The first clinical trials would appear to indicate that tolerance induction in humans using donor-derived cells is a relatively safe solution that is both promising and realistic.
输注供体来源的细胞可提高动物模型中器官移植的存活率。在某些情况下，它甚至可以诱导免疫耐受（即无需任何维持性免疫抑制治疗即可实现器官长期存活）。使用非清髓性方案可使供体来源的骨髓细胞植入，诱导混合嵌合体形成，并使啮齿动物产生免疫耐受。高剂量的骨髓细胞与抗T细胞抗体一起使用，甚至可以在不进行细胞清除性宿主预处理的情况下导致混合嵌合体形成。培养的供体来源的CD34+细胞或与针对共刺激分子的单克隆抗体相关的供体来源的未成熟（甚至成熟）树突状细胞也可能诱导免疫耐受。在众多导致动物模型中实体器官免疫耐受的实验方案中，我们如何在人类移植中找到方向？众多问题尚待解决：所用供体来源细胞（包括基质细胞）的类型和数量、与器官移植同步输注供体细胞的时机、输注途径（应是静脉内、门静脉内？）以及预处理方案。首批临床试验似乎表明，使用供体来源的细胞诱导人类免疫耐受是一种相对安全的解决方案，既具有前景又切实可行。
