以嵌合体为基础的器官移植操控性免疫耐受的研究进展

Progress of chimerism-based manipulate immune tolerance in organ transplantation

移植物的免疫耐受是器官移植领域的最终目标。尽管在小鼠器官移植中报道了诸多诱导免疫耐受的方案,但迄今为止,基于造血干细胞移植的嵌合体方案是人类肾移植中诱导免疫耐受的唯一可重复性方案。通过短暂的混合嵌合或稳定的完全嵌合均可诱导移植肾免疫耐受。尽管持久的完全嵌合状态可能会降低移植肾发生排斥反应的风险,但移植物抗宿主病(graft-versus-host disease,GVHD)的出现限制了此方案的广泛临床应用。相反,短暂的混合嵌合不会导致GVHD的发生,但造血干细胞嵌合消失后很难预测移植物排斥反应的风险。目前的努力旨在开发临床上更可行和可靠的方法来诱导持久的混合嵌合体,以便扩大这些治疗方案的临床适用性。

The tolerance of allograft has been considered the ultimate goal in organ transplantation. Although numerous protocols of allograft tolerance induction have been reported in mice,thus far,chimerism based on hematopoietic stem cell transplantation is the only reproducible scheme for inducing immune tolerance in human kidney transplantation. Transient immune chimerism or stable chimerism could induce renal allograft tolerance. Although persistent complete chimerism may reduce the risk of rejection,the development of graft-versus-host disease( GVHD) has limited its wide clinical application. In contrast,short-term mixed chimerism does not lead to GVHD,but it is difficult to predict the risk of graft rejection after the disappearance of hematopoietic stem cell chimerism. Current efforts are aimed at developing clinically more feasible and reliable methods to induce persistent mixed chimeras in order to expand the clinical applicability of these treatment regimens.