Immunological assessment of peripheral lymphocytes of patientsafter living related liver transplantation

我们已经减少了活体相关肝移植(LRLT)后肝功能稳定和正常的患者的免疫抑制。为了对LRLT后患者进行免疫学分析，我们测定了供者和第三方患者移植前混合淋巴细胞反应(MLR)流出液中Th1细胞因子(IL-2、干扰素)的水平，供者MLR流出液中IL-2和干扰素的平均值(分别为3.8pg/ml和24.1pg/ml)明显低于第三方(分别为27.5pg/ml和88.2pg/ml)。移植前对相关供者的低反应性可能是由于HLA半相合组合可能是LRLT与身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和正常的患者进行MLR。小剂量免疫抑制患者的IL-2和干扰素流出水平高于大剂量患者。此外，与第三方相比，这些患者对捐赠者的低反应性仍然存在。提示只要肝功能稳定，MLR出水中细胞因子水平较高，就可以减轻免疫抑制。目前，基于这一发现，一项前瞻性减少免疫抑制的方案被成功地实施。3)7名肝功能稳定和正常但没有免疫抑制的患者进行MLR。提示临床耐受患者的外周血淋巴细胞对供者无获得性耐受。为了阐明耐受的机制，还需要进一步研究接受器官中的免疫反应，包括人类白细胞抗原的表达。

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.