Induction of tolerance in the pig-to-human Xenotransplantation by using Xenoreactive antibody producing B cells and Xenoantigen.

使用产生异种反应抗体的 B 细胞和异种抗原诱导猪对人异种移植的耐受性。

• 批准号: 11671143
• 负责人: SATOMI Susumu
• 金额: $ 2.56万
• 依托单位: TOHOKU 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 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671143/
• 关键词: xeno-reactive national antibody; porcine thyroglobulin; Gal-1, 3-Gal; splenectomy; graft survival; ブタのサイログロブリン; 抗体産生細胞; 液性拒絶反応; サイログロブリン; 免疫抑制剤; IgMI; IgD; IgG; CD5

Experimental study 1To examine the distribution of the xeno-reactive national antibody (XNA)-producing B cells in humans, we obtain the lymphocytes from the spleen tonsilla gland and peripheral blood. For the immunoselection of XNA-producing cells, we used magnetic beads coated with porcine thyroglobulin (PTg) which expressed Gal-1, 3-Gal terminal residues. It was confirmed by FACS analysis that almost all cells selected by PTg beads showed the presence of the CD20. On an experiment of transforming EBVto PTg-beads -selected B cells and normal B cells, although only 10% of the normal B cells showed XNA, 44% of the wells showed XNA in PTg-bead selected B cells. The overall expression rate of CD5 on XNA producing B cells was not significantly different to that n non-separated B cells. The expression rate of sIgM and sIgD on XNA-producing B cells was significantly higher than that on non-separated B cells.Experimental study 2Hamster hearts were transplanted to 2 colonies of Lewis rats and nude rats. CyA was given and splenectomy (Spx) was performed on the day of transplantation in same groups. The combined treatment of Spx and CyA showed a significant increase in graft survival time. Spx reduced Xab production to undetectable level in CyA treated Lewis rats and nude rats.

实验研究1为了检测产生异种反应性国家抗体（XNA）的B细胞在人体中的分布，我们从脾扁桃体和外周血中获得淋巴细胞。对于产生XNA的细胞的免疫选择，我们使用用表达Gal-1，3-Gal末端残基的猪甲状腺球蛋白（PTg）包被的磁珠。通过FACS分析证实，几乎所有通过PTg珠选择的细胞都显示出CD 20的存在。在将EBV转化为PTg-珠选择的B细胞和正常B细胞的实验中，尽管仅10%的正常B细胞显示XNA，但在PTg-珠选择的B细胞中44%的威尔斯显示XNA。产生XNA的B细胞上的CD 5的总体表达率与未分离的B细胞上的CD 5的总体表达率没有显著差异。产生XNA的B细胞上sIgM和sIgD的表达率明显高于未分离的B细胞。实验研究将25只大鼠心脏移植到刘易斯大鼠和裸大鼠的两个群体中。移植当天给予CyA并行脾切除术（Spx）。Spx和CyA的联合治疗显示移植物存活时间显著增加。在CyA处理的刘易斯大鼠和裸大鼠中，Spx将Xab产生降低至检测不到的水平。

项目成果

J.Takayama, et al.: "Long Term Survivals in Hamster to Rat Cardiac Xenotransplantation Using Cyclosporine a Alone"Xenotransplantation. (in press). (2001)

J.Takayama等人：“单独使用环孢素a的仓鼠至大鼠心脏异种移植中的长期存活”异种移植。