Tolerance induction by biological modulation in allogeneic and xenogeneic

本研究旨在分析仓鼠-大鼠异种移植受者的显微嵌合体（MC），并评估供体骨髓（DBM）增强对异种移植存活的影响。为了评估异种器官移植后MC的生物学相关性，我们将肺和心脏受者分为三组：1组未经治疗；2组给予短期疗程的环磷酰胺FK506；第三组给予长期免疫抑制剂治疗。在这些组中，MC随肺移植排斥反应的进展而平行变化，而在心脏移植中未检测到。第3组MC动态变化；一旦消失，就会在两个器官中增加。这种延迟的MC发育表明受体中存在具有造血干细胞特征的供体乘客白细胞。仓鼠肝/心异种移植后立即输注DBM （2.OX108）。接受者分为四组：第一组未经治疗；第二组灌胃DBM；3组给予a（肝脏：FK506 /心脏：环磷酰胺和FK506）；第4组给予DBM和短期免疫抑制剂治疗。两脏器中，4组的MST均明显长于3组。肝移植术后外周血MC状态持续时间4组明显长于3组。心脏3组仅4组持续观察MC至第30天。综上所述，这些研究结果表明，在没有长期免疫抑制治疗的情况下，伴随的DBM增强促进了MC，并显着延长了异种移植物的生存期。但在本研究中，MC不持久，无法实现持久的移植物接受。为了制造持久的异种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.