Analysis of rejection mechanism, aiming for the establishment of novel immunosuppression in small bowel transplantation

背景资料：临床活体小肠移植的经验促使我们对以下问题进行研究，这些问题一直是提高移植物和/或患者存活率的障碍：早期和明确的排斥反应诊断更复杂的方法来控制排斥反应猪SBT模型：猪是我们的实验，因为人类和猪之间的解剖，生理和免疫学相似。我们建立了猪原位SBT模型，供受者均表现为同种异体混合淋巴细胞反应。标本采集：a）经中心静脉给药和采血b）纤维镜检查（使用临床儿科纤维）和活检。我们建立了猪原位SBT模型，并安全、定期地进行这些技术，使我们能够在临床移植的同一水平上监测排斥反应过程。结果：根据肉眼和显微镜下的发现，排斥反应的严重程度，免疫排斥反应的严重程度。 ...更多信息 结果表明，排斥组移植物的凋亡小体计数（ABC）（6.59/10个）高于非排斥组（0.773/10个），差异有统计学意义。免疫组化法分析细胞凋亡的诱导途径。CD 8+淋巴细胞和FasL+淋巴细胞浸润的隐窝周围和上皮细胞上的TNF受体的表达增加，同时，或之前，宏观和/或组织学rejection.Future的前景和计划：在猪SBT的排斥反应，现在可以更详细地分析与上述指标。利用这些指标，我们正在进行进一步的研究项目，如局部施用免疫抑制剂或诱导耐受。这些指标将应用于我们未来的临床SBT病例的排斥反应的诊断。少

Background : The experience with clinical living donor SBT(small bowel transplantation) motivate us to research on the following problems, which have been the obstacles to the improvement of graft and/or patient survival.Earlier and definite diagnosis of rejectionMore sophisticated way to control rejectionPig SBT model : Pigs are adopted for our experiment because of the anatomical, physiological and immunological similarity between humans and pigs. We established one-staged orthotopic SBT model using donors and recipients which showed alloreactivity with mixed lymphocyte reaction.Sampling of specimens :a) drug administration and blood sampling through central lineb) fiberscopy (using clinical pediatric fiber) and biopsyWe established techniques above with pig SBT model and are performing these safely and regularly, which enable us to monitor the rejection process at the same level for clinical transplantation.Results : Based on the macroscopic and microscopic findings, severity of rej … More ection and its relationship to ABC (apoptotic body counts) were analyzed under the immunosuppression with Tacrolimus, which has been the key drug for clinical SBT.Samples from grafts with rejection presented higher ABC (6.59/l0crypts) than those from non-rejected grafts (ABC ; 0.773/l0crypts), which showed statistical difference. There was no correlation between the severity of rejection and ABC.Immunohistochemical studies were performed to analyze the induction pathway to apoptosis. Infiltration of CD8+ lymphocytes and FasL+ lymphocytes around crypts and increased expression of TNF receptor on epithelial cells were observed at the same time with, or prior to, macroscopic and/or histological rejection.Future prospects and plans : The rejection in pig SBT now can be analyzed more in detail with the indicators above. Using the indicators, we are moving on to the further research projects such as local administration of immunosuppressants or tolerance induction. These indicators will be applied for our coming clinical SBT cases for the diagnosis of rejection. Less