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Mechanisms of Mixed Chimerism-Based Transplant Tolerance
Trends in Immunology ( IF 16.8 ) Pub Date : 2017-08-18 00:00:00 , DOI: 10.1016/j.it.2017.07.008
Julien Zuber,Megan Sykes

Immune responses to allografts represent a major barrier in organ transplantation. Immune tolerance to avoid chronic immunosuppression is a critical goal in the field, recently achieved in the clinic by combining bone marrow transplantation (BMT) with kidney transplantation following non-myeloablative conditioning. At high levels of chimerism such protocols can permit central deletional tolerance, but with a significant risk of graft-versus-host (GVH) disease (GVHD). By contrast, transient chimerism-based tolerance is devoid of GVHD risk and appears to initially depend on regulatory T cells (Tregs) followed by gradual, presumably peripheral, clonal deletion of donor-reactive T cells. Here we review recent mechanistic insights into tolerance and the development of more robust and safer protocols for tolerance induction that will be guided by innovative immune monitoring tools.

中文翻译:

基于混合嵌合体的移植耐受机制

对同种异体移植物的免疫反应是器官移植的主要障碍。避免慢性免疫抑制的免疫耐受性是该领域的关键目标,最近在临床上通过在非清髓性条件治疗后将骨髓移植(BMT)与肾脏移植结合起来实现了这一目标。在高水平的嵌合体中,这种方案可以允许中央缺失耐受,但是具有移植物抗宿主(GVH)疾病(GVHD)的显着风险。相比之下,基于瞬时嵌合体的耐受性没有GVHD风险,并且似乎最初依赖于调节性T细胞(Tregs),随后逐渐地,大概是外周性的供体反应性T细胞克隆性缺失。
更新日期:2017-09-20
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