Analysis of mechanisms in delayed xenograft and cellular rejection in xenotransplant between human and swine

人猪异种移植延迟异种移植和细胞排斥的机制分析

• 批准号: 11671588
• 负责人: SHIROKI Ryoichi
• 金额: $ 1.92万
• 依托单位: Fujita Health University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671588/
• 关键词: Xenotransplantation; Organ Transplantation; Transplant Immunology; Chronic Rejection; Rejection; T細胞; SCIDマウス; 血管内皮細胞

Humanized severe combined immunodeficient (SCID) mice, which exhibited human immunological environment, were established by administration of human peripheral blood lymphocytes (PBL). This hu-PBL-SCID mice were also demonstrated to involve functional human lymphocyte and immunoglobulin in their circulation. To display the real xenotransplant circumstances from swine graft to human in mouse, swine mesenteric arterior was applied for direct bypass of abdominal aorta in hu-PBL-SCID. Analysis of recovered xenograft revealed human IgM adherence to inner rim and lymphocytes invasion on the endothelium of the xenograft. By blocking the xenoreactive serological response with immuno-absorption, pathological analysis indicated these lymphocytes belonged to human CD3+CD4+ in staining. Next, we tried to determine the optimal time to see the cellular rejection in the severest condition by changing the recovering time of xenograft. Stable model of the cellular rejection were.however, difficult to es … More tablish due to the interindividual differences. Human lymphocytes were unable to be detected in the invasion into swine arterior xenografts. We also tried to contitute the human xenoreactive cell line in vitro by recovering this xenografts to tissue culture using irradiated pig aortic endothlial cell (PAEC) as stimulator and irradiated original human lymphocytes as feeder. This experiment, however, resulted in impossible condition due to contaminations from grafts.Recently Dr.Sasaki, one of our colleagues, showed that human NK cells recognized non-expression of HLA-G ＆ E gene in xenograft and played a role in xenograft rejection (Transplantation 67; 31-37 1999). We tried to indicate this evidence in in vivo system using hu-PBL-SCID mice model. Swine arterior xenogarfts transfected with HLA-G ＆ E gene were recovered from hu-PBL-SCID mice, but no suppressive effect of xenoreactive responses were noted in this experoment. One of our manuscripts containing these results were now (in press). Less

采用人外周血淋巴细胞（PBL）诱导建立了人源化严重联合免疫缺陷（SCID）小鼠模型。该hu-PBL-SCID小鼠也被证明在其循环中涉及功能性人淋巴细胞和免疫球蛋白。为展示猪-人异种移植的真实的情况，采用猪肠系膜动脉直接转流法建立了人外周血淋巴细胞联合免疫缺陷模型（hu-PBL-SCID）。对回收的异种移植物的分析显示人IgM粘附于异种移植物的内缘和淋巴细胞侵入异种移植物的内皮上。通过免疫吸附阻断异种反应性血清学反应，病理学分析表明这些淋巴细胞在染色上属于人CD 3 + CD 4+。其次，我们试图通过改变异种移植物的恢复时间来确定在最佳条件下观察细胞排斥反应的最佳时间。稳定的细胞排斥模型，但难以建立， ...更多信息 由于个体间的差异。人淋巴细胞在猪动脉移植物中的浸润未被检测到。我们还尝试用辐照猪主动脉内皮细胞（PAEC）作刺激细胞，辐照人淋巴细胞作饲养细胞，将异种移植物回收培养，在体外建立人异种反应性细胞系。最近，我们的同事Sasaki博士表明，人类NK细胞识别异种移植物中HLA-G & E基因的非表达，并在异种移植物排斥中发挥作用（Transplantation 67; 31-37 1999）。我们试图在使用hu-PBL-SCID小鼠模型的体内系统中表明这一证据。从hu-PBL-SCID小鼠体内回收了转染HLA-G & E基因的猪动脉异种移植物，但未观察到异种反应的抑制作用。我们的一份包含这些结果的手稿现在正在印刷中。少

项目成果

白木良一, 星長清隆: "腎移植慢性拒絶反応の病態と治療"泌尿器科紀要. (印刷中).

Ryoichi Shiraki，Kiyotaka Hoshinaga：“慢性肾移植排斥的病理学和治疗”泌尿外科通报（正在出版）。