Clinical, immunological, and pathological aspects of operational tolerance after pediatric living-donor liver transplantation
Clinical, immunological, and pathological aspects of operational tolerance after pediatric living-donor liver transplantation
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DOI：
10.1016/j.trim.2006.10.004
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发表时间：
2007-02-01
影响因子：
1.5
通讯作者：
Uemoto, Shinji
中科院分区：
文献类型：
--
作者：
Koshiba, Takaaki;Li, Ying;Uemoto, Shinji
在我们的儿科活体肝移植（LDLT）中，87名患者（占所有患者的15.0%：与其他移植中心相比比例明显更高）实现了完全撤除免疫抑制，这被称为“手术耐受”。 54 名患者按计划完全停用免疫抑制剂，33 名患者因 EBV 感染或其他并发症而完全停用。对手术耐受患者的外周血进行的免疫学分析表明，发生了非缺失耐受，其中对供体抗原的潜在反应性 T 细胞物理上保留在免疫库中，但受到某些机制的特异性抑制。不仅耐受患者外周淋巴细胞中CD4(+)CD25(high+) T细胞的比例增加，并且特异性抑制供体抗原的MLR，而且耐受肝脏内存在表达FOXP3的细胞。因此，在解释非缺失耐受性的几种机制中，Tregs 可能至少部分涉及我们的耐受性患者。 V δ 1 γ δ T 细胞是γ δ T 细胞的一个子集，主要存在于肠道中，在成功妊娠期间会进入外周血，但在流产期间则不会。由于V delta 1 gamma delta T细胞产生大量IL-10，因此有人提出V delta 1 gamma delta T细胞通过促进Th2免疫偏差来诱导胎儿耐受。与妊娠一致，产生 IL-10 的 V delta 1 gamma delta T 细胞出现在耐受患者的血液中。这可能反映了胎母耐受性和移植耐受性之间的共同特征。我们从2003年1月开始对肝功能正常的LDLT后患者进行方案活检。与维持免疫抑制的患者相比，手术耐受的患者尽管肝功能正常，但表现出胆管尺寸减小和数量增加以及更大程度的纤维化。这使得即使在肝功能正常的情况下，在完全停止免疫抑制之前和之后也需要进行连续的活检。 (c) 2006 Elsevier B.V. 保留所有权利。
In the setting of our pediatric living-donor liver transplantation (LDLT), 87 patients (15.0% of all the patients: significantly higher proportion, compared with those of other transplant centers) achieved complete withdrawal of immunosuppression, which is referred to as "operational tolerance". Immunosuppressants were completely discontinued for 54 patients as scheduled, and for 33 because of EBV infection or other complications.Immunological analyses of the peripheral blood derived from operationally tolerant patients demonstrated that non-deletional tolerance takes place in which potentially reactive T cells to donor-antigens remain physically in the immune repertoire, but specifically suppressed by certain mechanisms. Not only CD4(+)CD25(high+) T cells were increased in the proportion in the tolerant patients' peripheral lymphocytes and suppressed MLR specifically to the donor antigen, but also FOXP3 expressing cells were present within the tolerant liver. Thus, among several mechanisms accounting for non-deletional tolerance, Tregs are likely to involve at least in part in our tolerant patients. V delta 1 gamma delta T cells, a subset of gamma delta T cells, which otherwise reside mainly in the intestine, emerge into the peripheral blood during successful pregnancy but not abortive pregnancy. Since V delta 1 gamma delta T cells produce massive IL-10, it is proposed that V delta 1 gamma delta T cells induce fetomatemal tolerance by promoting Th2 immune deviation. Consistent with pregnancy, IL-10 producing V delta 1 gamma delta T cells emerge into the blood of our tolerant patients. This may reflect a common feature between fetomatemal tolerance and transplant tolerance.We began protocol biopsy in post-LDLT patients who exhibit normal liver function from January 2003. Operationally tolerant patients, albeit showing normal liver function, exhibited decrease in size and increase in number of the bile duct and the fibrosis to a greater extent, compared with patients on maintenance immunosuppression. This warrants serial protocol biopsy before and after complete cessation of immunosuppression even in the presence of normal liver function. (c) 2006 Elsevier B.V. All rights reserved.