Immunological assessment of peripheral lymphocytes of patientsafter living related liver transplantation

活体肝移植术后患者外周淋巴细胞的免疫学评估

• 批准号: 07557249
• 负责人: TANAKA Koichi
• 金额: $ 1.86万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07557249/
• 关键词: living related liver transplantation; immunosuppression; tolerance; mixed lymphocyte reaction; cytokines; Tacrolimus; 肝移植

We have reduced immunosuppression of patients with stable and normal liver function after living related liver transplantation (LRLT). For immunological analysis in patients after LRLT, we measured Th1 cytokines (IL-2, IFN) in the effluent of mixed lymphocyte reaction (MLR) against lymphocytes of donors or third party persons.1)MLR patients before transplantation.The mean values of IL-2 and IFN in the effluent in MLR against donors ( 3.8 pg/ml and 24.1 pg/ml, respectively) were significantly lower than those against third party (27.5 pg/ml, 88.2 pg/ml, respectively). This hyporesponsiveness against related donors prior to transplantation presumably due to HLA haploidentical combination could be an advantage of LRLT compared to cadaveric transplantation.2)MLR in patients with stable and normal liver functions under immunosuppression longer than 2 years after transplantation.The effluent levels of IL-2 and IFN in patients with smaller doses of immunosuppression were greater than those in patients with larger doses. Further, the hyporesponsiveness against donors compared to the third party were remained in these patients. It is suggested that immunosuppression can be reduced as far as the liver functions are stable and the cytokine levels in the MLR effluent are high. Currently, a protocol of prospective reduction of immunosuppression is successfully carried out based on this findings.3)MLR in 7 patients with stable and normal liver functions with no immunosuppression.The cytokine levels in the effluent of MLR against donors are similar to those against third party. It is suggested that the peripheral lymphocytes of the patients in clinical tolerance do not acquired tolerance to donor. Further study focusing on the immunoreaction in the accepted organs including expression of HLA antigens is required to clarify the mechanism of the tolerance.

我们减少了活体相关肝移植（LRLT）后肝功能稳定且正常的患者的免疫抑制。对于LRLT后患者的免疫学分析，我们测量了针对供者或第三方淋巴细胞的混合淋巴细胞反应（MLR）流出物中的Th1细胞因子（IL-2、IFN）。1）移植前的MLR患者。针对供者的MLR流出物中IL-2和IFN的平均值（3.8 pg/ml和24.1） pg/ml）显着低于第三方（分别为 27.5 pg/ml、88.2 pg/ml）。移植前这种对相关供体的低反应性可能是由于 HLA 单倍体组合所致，这可能是 LRLT 与尸体移植相比的一个优势。2) 移植后 2 年以上免疫抑制下肝功能稳定正常的患者的 MLR。免疫抑制剂量较小的患者的 IL-2 和 IFN 流出物水平高于免疫抑制剂量较大的患者 剂量。此外，与第三方相比，这些患者对捐赠者的反应仍然较低。建议只要肝功能稳定且MLR流出液中细胞因子水平较高，即可减轻免疫抑制。目前，基于这一发现，成功地实施了前瞻性减少免疫抑制的方案。3）7名肝功能稳定正常、无免疫抑制的患者进行了MLR。针对供体的MLR流出物中的细胞因子水平与针对第三方的相似。提示临床耐受的患者外周淋巴细胞并未获得对供者的耐受。需要进一步研究接受器官中的免疫反应，包括 HLA 抗原的表达，以阐明耐受的机制。

项目成果

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