Oura T, Cosimi A B, Kawai T
Department of Surgery, Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Clin Exp Immunol. 2017 Aug;189(2):190-196. doi: 10.1111/cei.12969. Epub 2017 Apr 20.
Induction of allograft tolerance has been considered the ultimate goal in organ transplantation. Although numerous protocols to induce allograft tolerance have been reported in mice, a chimerism-based approach through donor haematopoietic stem cell transplantation has been the only approach to date that induced allograft tolerance reproducibly following kidney transplantation in man. Renal allograft tolerance has been achieved by induction of either transient mixed chimerism or persistent full donor chimerism. Although the risk of rejection may be low in tolerance achieved via durable full donor chimerism, the development of graft-versus-host disease (GVHD) has limited the wider clinical application of this approach. In contrast, tolerance induced by transient mixed chimerism has not been associated with GVHD, but the risk of allograft rejection is more difficult to predict after the disappearance of haematopoietic chimerism. Current efforts are directed towards the development of more clinically feasible and reliable approaches to induce more durable mixed chimerism in order to widen the clinical applicability of these treatment regimens.
诱导同种异体移植耐受一直被视为器官移植的最终目标。尽管在小鼠中已报道了许多诱导同种异体移植耐受的方案，但通过供体造血干细胞移植实现的基于嵌合体的方法是迄今为止唯一能在人类肾移植后可重复诱导同种异体移植耐受的方法。通过诱导短暂混合嵌合体或持续完全供体嵌合体已实现了肾移植耐受。尽管通过持久完全供体嵌合体实现的耐受排斥风险可能较低，但移植物抗宿主病（GVHD）的发生限制了该方法更广泛的临床应用。相比之下，短暂混合嵌合体诱导的耐受与GVHD无关，但造血嵌合体消失后同种异体移植排斥的风险更难预测。目前的努力方向是开发更具临床可行性和可靠性的方法，以诱导更持久的混合嵌合体，从而扩大这些治疗方案的临床适用性。
