Tolerance induction by biological modulation in allogeneic and xenogeneic

本研究旨在分析金黄地鼠至大鼠异种移植受者的微循环(MC)，并评价供者骨髓(DBM)扩增对异种移植存活的影响。我们建立了用聚合酶链式反应(PCR)检测金黄地鼠异种器官移植后MC的方法，以评估器官异种移植后MC的生物学相关性。受者分为3组：I组不治疗，2组接受环磷酰胺FK506短程治疗，3组接受长程免疫抑制剂治疗。在这些组中，MC的变化与肺移植物中排斥反应的进展平行，而在心脏移植物中检测不到。第3组MC动态变化，两个脏器MC消失后增加。MC发育迟缓提示受者体内存在具有造血干细胞特征的供者外周血白细胞。金黄地鼠DBM(2.OX108)在肝脏/心脏异种移植后即刻输注。受者分为4组：第1组为未治疗组，第2组为DBM组，第3组为a组(肝脏：FK506/心：环磷酰胺+FK506)，第4组为DBM+短程免疫抑制剂。肝移植后，4组大鼠外周血中MC状态持续时间明显长于3组。在心脏3组，只有4组连续观察到MC，直到第30天。综上所述，这些发现表明，在没有长期免疫抑制治疗的情况下，伴随的DBM增加促进了MC的形成，并显著延长了异种移植的存活时间。但在本研究中，MC不是持久的，无法实现长期的移植物接受。为了制造出持久的异种MC，还需要进一步的研究。

This study was designed to analyze the microcimerism (MC) in the hamster-to-rat xenografted recipients, and to evaluate the effect of donor bone marrow (DBM) augmentation on xenograft survival. We established the method using PCR for detection of MC in hamster-to-rat combination To assess the biological relevance of MC after organ xenotransplantation, both lung and heart recipients were divided into three groups : group I were untreated ; group 2 received short course of cyclophosphamide FK506 ; and group 3 were treated with a long course of immunosuppressants. In these groups, MC changed in parallel with the progression of rejection in lung grafts, whereas it was not detected in heart grafts. In group 3, MC changed dynamically ; once disappeared and then it increased in both organs. This delayed development of MC suggests the existence of donor passenger leukocytes in the recipients that had the character of the hematopoietic stem cells. Hamster DBM (2.OX108) were infused immediately after liver/heart xenotransplanration. Recipients were divided into four groups : group 1 were untreated ; group 2 were infused with DBM ; group 3 received a (liver : FK5O6/heart : cyclophosphamide and FK506) ; and group 4 were infused with DBM and short course of immunosuppressants. In both organs MST for group 4 were significantly longer than that for group 3. The duration of the MC state in the peripheral blood was clearly longer in group 4 thanin group 3 after liver transplantation. In heart group 3, MC was observed in only group 4 continuously until day 30. In conclusion, these findings suggest that concomitant DBM augmentation promoted MC in and markedly prolonged the xenograft survival without long standing immunosuppressive therapy. But in this study, MC was not persistent, and long-lasting graft acceptance could not be achieved. In order to make persistent xenogeneic MC, further studies are required.