Analysis and clinical application of donor specific immunohyporesponsiveness using intraportal injection of myeloid dendritic cells in small bowel transplantation

我们曾报道骨髓细胞是比外周血单个核细胞更强的诱导供体特异性低反应的效应细胞。在小肠移植（SBT）模型中，门静脉注射作为供体抗体的给药途径比外周血管注射更有效。即使在门静脉SBT移植手术的同时进行骨髓移植（BMT），诱导效率也没有降低，也没有引起阻碍移植的预适应。为了提高大鼠SBT模型骨髓移植获得特异性免疫抑制的效率，我们计划骨髓树突状细胞的分离、培养、成熟控制和移植实验。结果表明，在DAYO移植中诱导供体特异性低反应的主要细胞群是未成熟树突状细胞。而且，虽然未成熟树突状细胞治疗显著延长了大鼠SBT的移植物存活，但发现在具有成熟细胞的BMT中发生致命的GVHD，并且在更安全的临床应用中，需要进一步检查以维持培养的树突状细胞的分化。

We have been reported that bone marrow cells were stronger effector cells than peripheral mononuclear cells in induction of donor specific hyporesponsiveness. And portal injection as administration route of donor antibody was more efficient than peripheral vessels with a small bowel transplantation (SBT) model. Even bone marrow transplantation (BMT) was given at the same time with the transplant surgery of SBT in the portal vein, induction efficiency didn't decrease, and the presensitization which obstructed transplantation was not caused. In order to increase the efficiency of the peculiar immune suppression acquisition by BMT with a rat SBT model, we planned bone marrow dendritic cell isolation, cultivation, maturation control and transplant experiments. It was confirmed that the main population of the induction of donor specific hyporesponsiveness was immature dendritic cell in the DAYO transportal BMT in SBT. And, though treatment by the immature dendritic cell significantly prolonged the graft survival of the rat SBT, it was found out that fatal GVHD was made to occur in BMT with the mature cell, and further examination could be necessary to the maintenance of a differentiation of cultured dendritic cell in the safer clinical application.