Comparative study of immunological tolerance in the liver transplantation from cadaver and living donor

微嵌合已被认为在移植患者对同种异体器官移植的长期接受和维持供体特异性低反应状态中发挥重要作用。为了阐明嵌合发展的动力学，我们对活体相关肝移植（LRLTx）患者进行了随访分析。采用供体特异性HLA-DRB1引物对或Y染色体特异性序列引物，对移植后前6个月和18个月采集的血液样本和1个月采集的切片进行PCR分析供体细胞的存在。此外，在两个不同的时间点对LRLTx术后2年以上的长期患者进行了研究。在后续研究中，供体细胞可以在移植后立即出现在所有患者的血液中。在逐渐下降后，所有患者在几周或几个月内嵌合阴性。然而，在6个月时，63%的供体细胞重新出现，在18个月时，66%的供体细胞重新出现。这种嵌合发展的双相模式反映了受体中不同供体来源细胞群的发生。发生第二波嵌合的细胞群可能是由供体来源的具有干细胞潜能的细胞产生的，这些细胞位于移植物中或从移植物中迁移出来的受体造血器官中。这里研究的儿科患者群体接受了来自父母一方的单倍相同的移植物。因此，组织相容性的程度比大多数其他接受器官大小和ABO血型匹配而非HLA抗原匹配的尸体供者的肝脏移植患者要好得多。尽管存在这种差异，嵌合的发生率与尸体器官接受者的嵌合发生率非常相似。此外，我们没有发现皮肤或血液中可检测嵌合的发展与临床病程或免疫抑制需求之间存在明确的相关性。少

Microchimerism has been suggested to play an important role in the long-term acceptance of allogenic organ grafts by transplant patients and for the maintenance of a state of donor-specific low responsiveness. In order to elucidate the kinetics of the development of chimerism we have performed a follow-up analysis in patients with living-related liver transplantation (LRLTx). Blood samples obtained during the first 6 months and at 18 months post-transplant and slin biopsies taken at one month were analysed for the presence of donor cells by PCR using donor-specific HLA-DRB1 primer pairs or primers for a Y chromosome-specific sequence. Furthermore long-term patients more than 2 years after LRLTx were studied at two different time points. In the follow-up studies donor cells could be demonstrated in the blood of all patients immediately after transplantation. After a gradual decline all patients became chimerism negative for several weeks or months. At 6 months, however, 63% of them and … More at 18 months in 66% of them donor cells had reappeared. This biphasic pattern in the development of chimerism is proposed to reflect the occurrence of different donor-derived cell populations in the recipients. The cell population of cells occurring with the second wave of chimerism is likely to have been generated by donor-derived cells with stem cell potential located in the graft or in the hematopoetic organs of the recipient after emigration from the graft. The pediatric patient population studied here received haplo-identical graft from one of their parents. Thus the degree of histocompatibility is much better than in most other liver grafted patients receiving organs from cadaveric donors matched only for organ size and ABO blood groups but not for HLA antigens. Despite this difference, the incidence of chimerism was very similar to that found in recipients of cadaveric organs. Furthermore, we did not find a clear correlation between the development of detectable chimerism in skin or blood and the clinical course or the requirement for immunosuppressions. Less