TORELANCE INDUCTION AND IMMUNOSUPPRESSIVE STERATEGY OF SMALL BOWEL TRANSPLANTATION.

小肠移植的 TOrelance 诱导和免疫抑制策略。

• 批准号: 12671741
• 负责人: KANEHIRO Hiromichi
• 金额: $ 1.92万
• 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: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671741/
• 关键词: small bowel transplantation; mesenteric lymph node; apoptosis; cytokines; co-stimulatory molecule; graft associated lymphoid tissues; 拒絶反応; 肝小腸移植; ラット小腸移植; cathepsin S

Background. The high proportions of lymphoid tissues are one of underlying factors inducing severe rejection of small bowel transplantation. Mesenteric lymph nodes (MLN) contained in bowel graft are not only a source of donor- erived antigen-presenting cells, but also offer a field for immune reaction between donor and host. Methods. Heterotopic rat bowel transplantations were performed from BN donors to LEW recipients. In FK group (FK-G), recipients were given 0.5mg/kg FK506 I.m. for 28 days. Recipients without immunosuppression served as controls. On days 1, 4 and 7, graft and MLNs were taken for analysis from recipients of each group. Tissue samples of recipients of FK-G were divided for histology, TUNEL assay, flowcytometry, and RT-PCR. Results. All of the control group were rejected by day 10, while FK-G survived for longer than 100 days. FK protected the graft from acute rejection, while chronic rejection. The TUNEL assay in graft MLNs of FK-G, apoptotic cells were few, which was … More comparable to that in MLNs of naive animals. Apoptotic cells of control increased till day 4. In control, 30% of cells in MLNs were replaced by recipient-derived cells on day 1. The recipient cells reached up to 70% by day 4. On day 7, however, donor cells in MLNs of FK-G was 15%, which was significantly higher than control group. Among the host-type cells in the graft MLNs, CD8+ cells increased until day 7 in control. However, increase was not seen in FK-G. CD4+ cells in recipients without FK decreased after transplantation. The flowcytometry of donor MLN cells revealed expression of B7-1 and B7-2 was lower in FK-G than control at the early period. RT-PCR for cytokine mRNA showed up-regulation of IFN-g and IL-10 in MLNs of control from day 1. Such up-regulation appeared on day 4 in the graft jejunum. In FK-G, IFN-g and IL-10 disappeared by day 4 in MLNs. Interestingly, IFN-g, but not IL-10, reappeared in MLNs on day 30, while later up-regulation of IFN-g was absent until day 100. Conclusions. Immune responses in graft MLNs have impact on outcome of small bowel allograft. Apoptosis of graft MLN cells was well correlated with acute rejection. Modulation of co-stimulatory molecules on donor MLN and suppression of host CD8+ cells may control rejection after small bowel transplantation. Less

背景资料。高比例的淋巴组织是引起小肠移植严重排斥反应的潜在因素之一。移植物中的肠系膜淋巴结(MLN)不仅是供体获得的抗原提呈细胞的来源，而且为供体和宿主之间的免疫反应提供了场所。方法：研究方法。采用BN供体与LEW受体进行大鼠异位肠移植。FK组(FK-G)：腹腔注射FK506 0.5 mg/kg。已经28天了。未接受免疫抑制的受者作为对照。于移植后第1、4、7天，取各组受者的移植物及MLN进行分析。对接受FK-G治疗的患者的组织标本进行组织学、TUNEL检测、流式细胞术和RT-PCR检测。结果。对照组在第10天全部排斥，而FK-G存活超过100天。FK保护移植物免受急性排斥反应，而慢性排斥反应。TUNEL法检测FK-G移植物MLN中，凋亡细胞较少，为…。这与幼稚动物的MLN中的结果更接近。对照组MLN中有30%的细胞在第1天被受体来源的细胞取代，第4天受体细胞已达70%，而在第7天，FK-G组MLN中供体细胞为15%，显著高于对照组。在移植物MLN中的宿主细胞中，CD8+细胞一直增加到第7天。而FK-G组则未见增加。无FK的受者移植后CD4+细胞减少。供体MLN细胞的流式细胞仪检测显示，FK-G早期B7-1和B7-2的表达低于对照组。细胞因子mRNA的RT-PCR检测显示，对照组MLN中的干扰素-g和IL-10的表达从第1天开始上调，而在移植空肠中的表达在第4天才开始上调。在FK-G组，第4天MLN中的干扰素-g和IL-10消失。有趣的是，干扰素-g，而不是IL-10，在第30天重新出现在MLN中，而后来直到第100天，干扰素-g的上调才消失。结论。移植物MLN的免疫反应对同种异体小肠移植的预后有影响。移植物MLN细胞的凋亡与急性排斥反应密切相关。共刺激分子对供体MLN的调节和对宿主CD8+细胞的抑制可能控制小肠移植后的排斥反应。较少