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肝移植中免疫抑制的撤除与耐受机制

Withdrawal of immunosuppression in liver transplantation and the mechanism of tolerance.

作者信息

Zhang Chi-Xian, Wen Pei-Hao, Sun Yu-Ling

机构信息

Institute of Hepatobiliary and Pancreatic Diseases, Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhengzhou University, School of Medicine, Zhengzhou 450052, China.

出版信息

Hepatobiliary Pancreat Dis Int. 2015 Oct;14(5):470-6. doi: 10.1016/s1499-3872(15)60411-8.

Abstract

BACKGROUND

Immunosuppression reagents have side effects and cause considerable long-term morbidity and mortality in patients after liver transplantation. Sufficient evidences showed that minimization or withdrawal of immunosuppression reagents does not deteriorate the recipient's immune response and physiological function and therefore, is feasible in some recipients of liver transplantation. However, the mechanisms are not clear. The present review was to update the current status of immunosuppression in liver transplantation and the mechanism of minimization or withdrawal of immunosuppression in liver recipients.

DATA SOURCES

We searched articles in English on minimization or withdrawal of immunosuppression in liver transplantation in PubMed. We focused on the basic mechanisms of immune tolerance in liver transplantation. Studies on immunosuppression minimization or withdrawal protocols and biomarker in tolerant recipients were also analyzed.

RESULTS

Minimization or withdrawal of immunosuppression can be achieved by the induction of immune tolerance, which may not be permanent and can be affected by various factors. However, accurately evaluating immune status post-transplant is a prerequisite to achieve individualized immunosuppression. Numerous mechanisms for immune tolerance have been found, including immunophenotypic shift of memory CD8+ T cells and CD4+ T cell subsets. Activation of the inflammasome through apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain (ASC) in dendritic cells is associated with rejection after liver transplantation.

CONCLUSIONS

Minimization or withdrawal of immunosuppression can be achieved by the induction of immune tolerance via different mechanisms. This process could be affected by immunophenotypic shift of memory CD8+ T cells and CD4+ T cell subsets, which may be correlated with activation of the inflammasome through ASC in dendritic cells.

摘要

背景

免疫抑制试剂具有副作用,会导致肝移植患者出现相当严重的长期发病率和死亡率。充分的证据表明,减少或停用免疫抑制试剂不会恶化受者的免疫反应和生理功能,因此,在一些肝移植受者中是可行的。然而,其机制尚不清楚。本综述旨在更新肝移植免疫抑制的现状以及肝移植受者免疫抑制减少或停用的机制。

数据来源

我们在PubMed上搜索了关于肝移植中免疫抑制减少或停用的英文文章。我们重点关注肝移植免疫耐受的基本机制。还分析了关于免疫抑制最小化或停用方案以及耐受受者生物标志物的研究。

结果

通过诱导免疫耐受可以实现免疫抑制的最小化或停用,免疫耐受可能不是永久性的,并且会受到各种因素的影响。然而,准确评估移植后的免疫状态是实现个体化免疫抑制的前提。已经发现了许多免疫耐受机制,包括记忆性CD8+T细胞和CD4+T细胞亚群的免疫表型转变。通过树突状细胞中含有C端半胱天冬酶募集结构域(ASC)的凋亡相关斑点样蛋白激活炎性小体与肝移植后的排斥反应有关。

结论

通过不同机制诱导免疫耐受可以实现免疫抑制的最小化或停用。这个过程可能会受到记忆性CD8+T细胞和CD4+T细胞亚群免疫表型转变的影响,这可能与树突状细胞中通过ASC激活炎性小体有关。

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