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

尸体肝移植与活体肝移植免疫耐受的比较研究

• 批准号: 08044278
• 负责人: YAMAOKA Yoshio
• 金额: $ 7.3万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for international Scientific Research
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 无数据
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08044278/
• 关键词: immunotolerance; micro-chmerism; donor-specific gene; MHC-class 1; NK cell; KIR

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

微嵌合体被认为在移植患者长期接受同种异体器官移植和维持供者特有的低反应性状态中发挥重要作用。为了阐明嵌合体发展的动力学，我们对活体相关肝移植(LRLTx)患者进行了随访分析。在移植后前6个月和18个月期间采集的血液样本和1个月时采集的Slin活组织标本进行了供体细胞的分析，方法是使用供体特定的HLA-DRB1引物对或Y染色体特定序列的引物进行聚合酶链式反应(PCR)。此外，LRLTx后超过2年的长期患者在两个不同的时间点进行了研究。在后续研究中，所有患者在移植后的血液中都能立即显示出供体细胞。在逐渐下降后，所有患者在几周或几个月的时间内嵌合体呈阴性。然而，在6个月时，63%的人和…在18个月时，66%的供体细胞再次出现。这种嵌合体发展的双相模式被认为是为了反映不同供体来源的细胞群体在受者中的出现。随着第二波嵌合体的出现，细胞群体很可能是由供者来源的细胞产生的，这些细胞具有干细胞潜能，位于移植物中或移居移植物后受者的造血器官中。这里研究的儿科患者接受了来自父母之一的单倍体相合的移植物。因此，组织相容的程度比大多数其他肝移植患者要好得多，这些患者接受的器官来自只匹配器官大小和ABO血型而不匹配HLA抗原的身体供者。尽管存在这种差异，嵌合体的发生率与身体器官受者非常相似。此外，我们没有发现皮肤或血液中可检测到的嵌合体的发展与临床病程或免疫抑制要求之间的明确相关性。较少

项目成果

M.Kume: "Ischemic preconditioning of the liver in rats:Implications of heat shock protein induction to increase tolerance of ischemia-reperfusion injury." J.lab.Cin.Med.123(3). 251-258 (1996)

M.Kume：“大鼠肝脏的缺血预处理：热休克蛋白诱导对提高缺血再灌注损伤耐受性的影响。”

Eiji Yamamoto: "Evaluating the significance of HLA class II genotype matching in living-related liver transplantation." Transplantation Immunology. 4. 144-150 (1996)

Eiji Yamamoto：“评估 HLA II 类基因型匹配在活体相关肝移植中的意义。”

T. Kiuchi: "Background of early intragraft immune activation and rejection in liver transplans recipients"Transplantation. 60(1). 49-55 (1995)

T. Kiuchi：“肝移植受者早期移植物内免疫激活和排斥的背景”移植。

Y. Inomata: "The evolution of immunosuppression with FK506 in pediatric living-realted liver transplantation"Transplantation. 61(2). 247-252 (1996)

Y. Inomata：“儿科活体肝移植中 FK506 免疫抑制的演变”移植。

Y.Yamaoka: "Safety of the donor in living related liver transplantation-Analysis of 100 parental donors." Transplantation. 59(2). 224-226 (1995)

Y.Yamaoka：“活体相关肝移植供者的安全性——100例父母供者的分析”。