Development of new immunosuppressive methods for organ transplantation targetting recognition of antigen and adhesive molecule

以抗原和粘附分子识别为目标的器官移植免疫抑制新方法的开发

• 批准号: 06454399
• 负责人: EGUCHI Shoji
• 金额: $ 4.42万
• 依托单位: NIIGATA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06454399/
• 关键词: Antigen recognition; Cell adhesion; Adhesion molecule; alpha betaT cell receptor; CD2; Transplantation; Immunosuppression; Cytokine; 抗T細胞受容体抗体; Rnase protection assay; 臓器移植; ラット異所性心移植モデル; ラット同所性腎移植モデル; 抗TCR抗体; 抗CD2抗体; 種特異的免疫寛容; リンパ球増殖反応

1. Allogeneic cardiac transplantation(1) Short-term preoperative treatment of rats with a mAb against alpha betaTCR completely prevented the rejection of cardiac allografts. The donor specific unresponsiveness to cardiac tissue was induced in treated rats.(2) In rejected models, TNFalpha, IFNgamma and IL-1beta cytokine m-RNA were expressed in the tissue from the rejecting allogeneic cardiac grafts but not in the treated allogeneic cardiac grafts.(3) Short-term treatment of rats with a mAb against adhesion molecule CD2 completely prevented the rejection of cardiac allografts. This immunosuppression was donor specific and maintained by anergy.2. Allogencic lung transplantationAllogeneic lung grafts were completery rejected on the 6th days. Treatment of rats with a mAb against alpha betaTCR delayd the beginning of rejection. But the treated lung grafts were rejected on the 9th days. The differentiation of antigenicity between lung and heart seemed to contribute to the survival.3. Xenogeneic cardiac transplantationIn the xenogeneic transplantation model of mouse to rat, we got the prolongation of graft survival. Using mAb against alpha betaTCR,15-deoxyspergualin and post-operative splenectomy, we found that xenogeneic cardiac graft survived 70 days.

1. (1)术前短期用抗α - β - cr单克隆抗体治疗大鼠可完全预防同种异体心脏移植的排斥反应。在治疗大鼠中诱导供体对心脏组织的特异性无反应。(2)在排斥模型中，TNFalpha、IFNgamma和il -1 β细胞因子m-RNA在排斥模型的同种异体心脏移植组织中表达，而在处理过的同种异体心脏移植组织中不表达。(3)用抗粘附分子CD2的单抗短期治疗大鼠可完全阻止同种异体心脏移植的排斥反应。这种免疫抑制是供体特异性的，并通过能量维持。同种异体肺移植：同种异体肺移植在第6天完全排斥。用抗α - β - atcr单克隆抗体治疗大鼠可延缓排斥反应的发生。但经处理的肺移植物在第9天出现排斥反应。肺和心脏之间抗原性的分化似乎有助于生存。异种心脏移植在小鼠到大鼠的异种心脏移植模型中，我们得到了移植物存活时间的延长。使用抗α - β - atcr、15-脱氧果皮灵和术后脾切除术的单抗，我们发现异种心脏移植存活70天。

项目成果

Masanori Tsuchida,et al: "Induction of specific unresponsiveness to cardiac allografts by short-term administration of anti-T cell receptor α β antibody" Transplantation. 57. 256-262 (1994)

Masanori Tsuchida 等人：“通过短期施用抗 T 细胞受体 α β 抗体诱导对心脏同种异体移植物的特异性无反应”，移植。

土田 正則ほか: "INDUCTION OF SPECIFIC UNRESPNSIVENESS TO CARDIAC ALLOGRAFTS BY SHORT-TERM ADMINISTRATION OF ANTI-T CELL RECEPTOR αβ ANTIBODY" TRANSPLANTATION. 57. 256-262 (1994)

Masanori Tsuchida 等人：“通过短期施用抗 T 细胞受体 αβ 抗体诱导心脏同种异体移植物的特异性无反应”57. 256-262 (1994)。

Tsuchida M,et al.: "Induction of specific unresponsiveness to cardiac allografts by short-term administration of anti-T cell receptor alpha beta antibody" Transplantation. 57. 256 (1994)

Tsuchida M 等人：“通过短期施用抗 T 细胞受体 αβ 抗体诱导对心脏同种异体移植物的特异性无反应”移植。

Hirahara H,et al.: "Long term survival of cardiac allografts in rats treated before and after surgery with monoclonal antibody to CD2" Transplantation. 59. 85 (1995)

Hirahara H 等人：“手术前后用 CD2 单克隆抗体治疗的大鼠心脏同种异体移植物的长期存活”移植。

Hiroyuki Hirahara,et al: "Long term survival of cardiac allografts in rats treated before and after surgery with monoclonal antibody to CD2" Transplantation. 59. 85-90 (1995)

Hiroyuki Hirahara 等人：“手术前后用 CD2 单克隆抗体治疗的大鼠同种异体心脏移植物的长期存活”移植。