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。高比例的淋巴组织是一个逐渐排斥的小肠，其中包含的一些YMPH节点（MLN）并不是捐赠者对供体的抗活细胞宿主。 RT-PCR。在第4天，在第4天，凋亡细胞的凋亡细胞在MLN中。第1天，有30％的CELN是IPINT衍生的细胞。受体细胞在第4天到达70％。在第7天，供体细胞， -g为15％，直到第7天都会增加。在FK-G中，-1和B7-2在早期的对照中低于对照。 4在FK-G中，IFN-G和IL-10在MLN中消失了。缺席的第100天