TORELANCE INDUCTION AND IMMUNOSUPPRESSIVE STERATEGY OF SMALL BOWEL TRANSPLANTATION.

背景淋巴组织的高比例是导致小肠移植严重排斥反应的潜在因素之一。移植肠中的肠系膜淋巴结不仅是供者来源的抗原提呈细胞的来源，而且为供者与宿主之间的免疫反应提供了场所。方法.从BN供体到LEW受体进行异位大鼠肠移植。FK组（FK-G组）：肌注FK 506 0.5mg/kg; 28天。没有免疫抑制的受体作为对照。在第1、4和7天，从每组的受体中取出移植物和MLN用于分析。对FK-G受体的组织样本进行组织学、TUNEL测定、流式细胞术和RT-PCR。结果对照组在第10天全部出现排斥反应，而FK-G存活超过100天。FK对急性排斥反应有保护作用，对慢性排斥反应有保护作用。TUNEL法检测FK-G组移植MLNs凋亡细胞较少， ...更多信息 与未处理动物的MLN中的类似。对照组凋亡细胞增加至第4天。在对照组中，MLN中30%的细胞在第1天被细胞来源的细胞取代。到第4天，受体细胞达到70%。而在第7天，FK-G组MLN中的供体细胞为15%，显著高于对照组。在移植MLN中的宿主型细胞中，CD 8+细胞在对照中增加直到第7天。然而，在FK-G中未观察到增加。未使用FK的受者移植后CD 4+细胞减少。流式细胞仪检测结果显示，FK-G组MLN细胞B7-1和B7-2的表达在早期低于对照组。细胞因子mRNA的RT-PCR显示，从第1天开始，对照MLN中IFN-g和IL-10上调。这种上调出现在第4天的移植空肠。在FK-G中，MLN中的IFN-g和IL-10在第4天消失。有趣的是，IFN-g，而不是IL-10，在第30天再次出现在MLN中，而随后直到第100天才出现IFN-g的上调。结论.移植MLN的免疫应答对小肠移植的结果有影响。移植MLN细胞凋亡与急性排斥反应密切相关。调节供体MLN上的共刺激分子和抑制宿主CD 8+细胞可以控制小肠移植后的排斥反应。少

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