Tolerance induction by selective inoculation of doner lymphocytes

通过选择性接种供体淋巴细胞诱导耐受

• 批准号: 08671380
• 负责人: HISANAGA Michiyoshi
• 金额: $ 1.47万
• 依托单位: Nara Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08671380/
• 关键词: Heart transplantation; tolerance; Cell ceparation

Introduction : A number of experimental studies have shown the induction and maintenance of specific unresponsiveness or tolerance using donor antigens. However, most approaches require pretransplant strategies which are not feasible in clinical transplantation. In this study, we attempted to establish the simultaneous strategy with transplantation.Objective : We evaluated the effect of donor lymphocyte subsets inoculation to prolong cardiac allograft survival.Methods : BN rats were used as donors and LEW rats were as recipients of heart transplantation. Lymphocyte subsets were prepared from BN spleen cells by using magnetic beads (Dynabeads). The purity of fractionated splepocyte subsets were 90% (B cell), 90% (CD4 Tcell) and 65% (CD8 T cell). Experimental 1 ; We injected donor splenocytes or lymphocyte subsets (2x 10') simultaneously with heterotopic heart transplantation. FK5O6 (0.5mg/kg, intramuscular treatment) was administered on day -1,0, and 1. Group 1 (no treatment), Group 2 (FK506 alone), Group 3 (splenocytes with FK506), Group 4 (CD4), Group 5 (CD8) and Group 6 (B cells). Experimental 2 ; We injected donor B cells (5x10') simultaneously with transplantation. FK506 (1mg/kg) was administered on days 0-2. Group 7 (FK506 alone) and Group 8 (B cells with FK506).Results : The graft survival time was as follows. Group 1 (n=5, 6.8*0.4 days), 2 (n=7, 13.7*2.7), 3 (n=7 15.7*5.3), 4 (n=7, 10.0*1.5), 5 (n=7, 10.4*1.6) and 6 (n=6, 19.5*4.4). Group 6 v.s.Group 2 (p=O.O14). Furthermore, Group 7 (n=3, 33.0*3.7) and Group 8 (n=4, 48.3*14.0).Conclusion : B lymphocytes were more effective than T cells in prolonging donor graft survival. We speculate that B cells might act as antigen presenting cells and inactivate T cells. However, the effect was limited and insufficient. If more clinically applicapable and feasible strategies using B cells are established, we may induce donor specific tolerance.

简介：许多实验研究表明，使用供体抗原诱导和维持特异性无反应性或耐受性。然而，大多数方法需要移植前策略，这在临床移植中是不可行的。目的：探讨供体淋巴细胞亚群接种对心脏移植存活的影响。方法：以BN大鼠为供体，LEW大鼠为受体，进行心脏移植。通过使用磁珠（Dynabeads）从BN脾细胞制备淋巴细胞亚群。分离的脾细胞亚群纯度分别为90%（B细胞）、90%（CD 4 T细胞）和65%（CD 8 T细胞）。实验一：在异位心脏移植的同时注射供者脾细胞或淋巴细胞亚群（2 × 10 ~ 6）。FK 5 O 6（0.5mg/kg，肌内给药）在第-1、0和1天给药。第1组（未处理）、第2组（仅FK 506）、第3组（含FK 506的脾细胞）、第4组（CD 4）、第5组（CD 8）和第6组（B细胞）。实验2：在移植的同时注射供体B细胞（5 × 10 - 6）。在第0-2天给予FK 506（1 mg/kg）。第7组（FK 506组）和第8组（FK 506 + B细胞组）。组1（n=5，6.8*0.4天）、组2（n=7，13.7*2.7）、组3（n=7，15.7*5.3）、组4（n=7，10.0*1.5）、组5（n=7，10.4*1.6）和组6（n=6，19.5*4.4）。组6对比组2（p= 0.014）。结论：B淋巴细胞比T细胞更能有效地延长供者移植物的存活时间。我们推测B细胞可能作为抗原提呈细胞和抗增殖T细胞。然而，效果有限且不足。如果能建立更多的临床应用和可行的B细胞策略，我们可能诱导供体特异性耐受。

项目成果

M.Sho,Y.Nakajima,M.Hisanaga: "Simultaneous inoculation of doner lynphocyte subsets with transprantation in a rat cardiac allograft model" Transplantation Proceedings. 30・7. 3876-3878 (1998)

M.Sho、Y.Nakajima、M.Hisanaga：“在大鼠心脏同种异体移植模型中同时接种供体淋巴细胞亚群”移植论文集 30・7（1998）。

M.Shc, M.Hisanaga, et al: "Simultaneous inoculation of donor lymphecytes subsets with transplantation in a rat cardiac allegraft model" Transplantation Proceedings. 3C・7. 3876-3878 (1998)

M.Shc、M.Hisanaga 等人：“在大鼠心脏同种移植模型中同时接种供体淋巴细胞亚群”移植论文集 3C·7（1998）。

M.Sho, M.Hisanaga, et al.: "Simultaneous inoculation of donor lymphocyte subsets with transplantation in a rat cancer allograft model" Transplantation Proceedings. 30-7. 3876-3878 (1998)

M.Sho、M.Hisanaga 等人：“在大鼠癌症同种异体移植模型中同时接种供体淋巴细胞亚群和移植”移植论文集。

M.Sho,Y.Nakajima,M.Hisanaga,et al: "Simultaneous inoculation of donor lymphocyte subsets with transplantation in a rat cardiac allograft model" Transplantation Proceedings. (in press). (1998)

M.Sho、Y.Nakajima、M.Hisanaga 等人：“大鼠心脏同种异体移植模型中供体淋巴细胞亚群的同时接种和移植”移植论文集。