Treg-based therapy and mixed chimerism in small intestinal transplantation: Does Treg + BMT equal intestine allograft tolerance?
Treg-based therapy and mixed chimerism in small intestinal transplantation: Does Treg + BMT equal intestine allograft tolerance?
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DOI：
10.1016/j.mehy.2010.08.035
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发表时间：
2011-01-01
影响因子：
4.7
通讯作者：
Bai, Xue
中科院分区：
文献类型：
--
作者：
Du, Jun-Feng;Li, Shi-Yong;Bai, Xue
小肠移植（SIT）是治疗终末期肠衰竭的有效方法，但移植物排斥反应和非特异性免疫抑制剂的毒性仍是SIT的主要局限性。通过建立混合嵌合体诱导SIT耐受被认为是解决这一问题的一种稳健方法。在使用供体骨髓移植（BMT）+共刺激阻断的非清髓性受体制备的啮齿动物模型中，同种异体反应性T细胞的缺失在沉默移植物排斥T细胞的效应功能中起主导作用。然而，这种对同种异体移植耐受的细胞基础的理解可能是不完整的。近年来的研究表明，调节性T细胞（Treg）可以促进异基因混合嵌合体的建立，并诱导供者特异性免疫耐受。基于Treg的治疗本身被认为是预防同种异体移植排斥反应的一种有前途的无毒方法。此外，近年来的研究表明，TGFAP不仅在控制急性和慢性排斥反应中发挥重要作用，而且可能有助于保护同种异体移植物免受缺血/再灌注损伤（ischemia/reperfusion injury，IRI）。因此，我们推测，供者骨髓与同种异体抗原特异性T细胞联合移植可能是诱导移植耐受的最有效方案之一，从而改善SIT的总体结局。尽管已经做了很多努力，但仍需要开发一种无毒性的临床应用方案。皇冠版权所有（C）2010由爱思唯尔有限公司出版。保留所有权利。
Small intestinal transplantation (SIT) is a convincing treatment selection for end-stage bowel failure, however, graft rejection and the toxicity associated with the use of non-specific immunosuppression remain the major limitations in SIT. Induction of SIT tolerance through establishment of mixed chimeras is regarded as a robust approach to solve this problem. In rodent models of nonmyeloablative recipient preparation using donor bone marrow transplant (BMT) + costimulatory blockade, deletion of alloreactive T cells played the dominant role in silencing the effector function of graft-rejecting T cells. However, such understanding of the cellular basis for allograft tolerance might be incomplete. Several recent studies demonstrated that regulatory T cells (Tregs) could promote the establishment of allogeneic mixed chimerism as well as the induction of donor-specific tolerance. Treg-based therapy in and of itself is proposed to be a promising non-toxic approach to prevent allograft from rejection. In addition, latest studies showed that, Tregs not only played a critical role in controlling both acute and chronic rejection, but also might contribute to the protection of allograft from ischemia/reperfusion injury (IRI). Taken together, we hypothesize that, co-transplant of donor bone marrow and Tregs specific for alloantigens might be one of the most effective regimens to induce transplantation tolerance, so as to improve the overall outcome of SIT. Although much efforts have been made, a deliberate protocol without toxicity still needs to be developed for the clinical application. Crown Copyright (C) 2010 Published by Elsevier Ltd. All rights reserved.