Liver transplant tolerance and its application to the clinic: can we exploit the high dose effect?
Liver transplant tolerance and its application to the clinic: can we exploit the high dose effect?
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DOI：
10.1155/2013/419692
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发表时间：
2013
影响因子：
--
通讯作者：
Bishop GA
中科院分区：
文献类型：
--
作者：
Cunningham EC;Sharland AF;Bishop GA
肝脏的耐受性早已被认识到，尤其是在移植方面。在一些实验模型和一定比例的临床移植接受者中，肝移植发生了自发的接受。肝移植的接受是供者抗原特异性耐受的结果，表现为对供者来源的其他移植物的耐受性扩大。肝移植耐受的诱导与多种因素有关，包括肝组织主要组织相容性(MHC)分子的释放、免疫抑制供体白细胞的补体以及肝细胞直接与抗原特异性T细胞相互作用和破坏的能力。肝脏的大组织块也被认为是细胞因子的接收器，有可能耗尽免疫反应。在这篇综述中，我们概述了来自实验模型和临床移植的越来越多的证据，这些证据支持大组织块和高抗原剂量在诱导耐受中的作用。我们还讨论了一种新的基因治疗方法，以利用这种剂量效应并诱导足够强大的抗原特异性耐受，以克服启动的T细胞记忆反应。
The tolerogenic properties of the liver have long been recognised, especially in regard to transplantation. Spontaneous acceptance of liver grafts occurs in a number of experimental models and also in a proportion of clinical transplant recipients. Liver graft acceptance results from donor antigen-specific tolerance, demonstrated by the extension of tolerance to other grafts of donor origin. A number of factors have been proposed to be involved in liver transplant tolerance induction, including the release of soluble major histocompatibility (MHC) molecules from the liver, its complement of immunosuppressive donor leucocytes, and the ability of hepatocytes to directly interact with and destroy antigen-specific T cells. The large tissue mass of the liver has also been suggested to act as a cytokine sink, with the potential to exhaust the immune response. In this review, we outline the growing body of evidence, from experimental models and clinical transplantation, which supports a role for large tissue mass and high antigen dose in the induction of tolerance. We also discuss a novel gene therapy approach to exploit this dose effect and induce antigen-specific tolerance robust enough to overcome a primed T cell memory response.
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影响因子：
4.4
作者：
He, CS;Schenk, S;Heeger, PS
通讯作者：
Heeger, PS
影响因子：
15.9
作者：
Bowen, DG;Zen, M;Bertolino, P
通讯作者：
Bertolino, P
DOI：
10.1111/j.1749-6632.1964.tb34700.x
发表时间：
1964-01-01
期刊：
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES-SERIES
影响因子：
--
作者：
BALLANTY.DL;STETSON, CA
通讯作者：
STETSON, CA
影响因子：
0.9
作者：
Gutiérrez, A;Crespo, M;Oppenheimer, F
通讯作者：
Oppenheimer, F
影响因子：
8.8
作者：
Creput, C;Durrbach, A;Charpentier, B
通讯作者：
Charpentier, B