Study of Renal Transplantation by a New Immunosuppressive Method

去年报道了通过转移化学修饰的同种异体抗原诱导耐受。为了分析这一机制，我们用RT-PCR方法检测了移植肾中T细胞相关的细胞因子的表达，在同种异体移植肾中未观察到细胞因子mRNA的表达。相比之下，同种异体移植物表现出Th 1（IL-2，γ-INF）和Th 2（IL-4，IL-10）相关细胞因子mRNA的表达。此外，与未处理的同种异体移植物相比，处理的同种异体移植物中IL-2 mRNA的表达较低。结果提示，免疫耐受的诱导可能与Th 1/Th 2功能的免疫导向有关。最近，一种新的免疫抑制剂FTY 720被开发出来。本实验研究了FTY 720的免疫抑制作用及其机制。该制剂引起本地大鼠外周血淋巴细胞显著减少，而其他白细胞无显著变化。通过口服FTY 720观察到移植肾存活率的提高。在 ...更多信息 有趣的是，用FTY 720预处理比移植后施用更有效。因为我们发现在接受FTY 720的长期存活大鼠中脾脏萎缩，所以尝试检测细胞凋亡。FTY 720处理的移植大鼠脾脏中未检测到细胞凋亡。此后，生产Th 1相关的细胞因子进行了检查，在脾排斥反应期间（移植后第5天）。用RT-PCR方法检测到IL-2 mRNA在未处理的移植大鼠脾脏中的表达，而用FTY 720处理的移植大鼠脾脏中IL-2 mRNA无表达。我们推测长期存活的大鼠可能需要脾脏功能的改变。在临床研究中，在接受FK 506的患者中进行了系列移植肾活检和FK 506的药代动力学研究。强调了FK 506血药浓度监测的重要性。应进行频繁的测量，以减少FK 506诱导的肾毒性。另一方面，我们分析了受者血液和皮肤中的微嵌合体，并与MLR反应进行比较。微嵌合体似乎与移植后MLR反应指数无关。需要进一步的研究来证实这一结果。为了监测排斥反应，在受者中测量血液HGE。排斥反应时血HGF有升高趋势。我们正在研究肝细胞生长因子在排斥移植物中的免疫染色定位。少

Induction of tolerance by transferrance of chemically modified alloantigens was reported last year. To analyze this mechanism, we examined T-cell associated cytokines within renal allografts in the tolerance model by RT-PCR.No expression of cytokines of mRNAs was observed in isografts. In contrast, allografts demonstrated expression of both Th1 (IL-2, gamma-INF) and Th2 (IL-4, IL-10) associated cytokines mRNAs. In addition, the expression of IL-2 mRNA in treated allografts was low compared with taht in untreated ones. This results suggested that induction of tolerance may be responsible for immunoredirection of Th1/Th2 function in allografts. Recently, a novel immunosuppressive agent, FTY720 is explored. We studied the immunosuppressive effect and mechanism of FTY720. This agent induced dramatic decrease of peripheral lymphocytes in native rats while other leukocytes showed no significant changes. Enhancement of renal allograft survival was observed by oral administration of FTY720. In … More terestingly, pretreatment with FTY720 was more effective than posttransplant administration. Detection for apoptosis was tried because we found atrophic spleens in long-term survival rats receiving FTY720. No apoptosis was detected in spleens of FTY720-treated transplanted rats. Thereafter, production Th1 associated cytokines was examined in spleens during rejection (posttransplant day 5). We detected IL-2 mRNA in spleens of untreated transplanted rats by RT-PCR.However, no expression of this mRNA in spleens of treated transplanted rats with FTY720. We speculated that long-term survival rats may require functional change of spleens. In the clinical study, serial biopsies of renal grafts and pharmacokinetics study of FK506 were carried out in patients receiving FK506. We emphasized the immportance of monitoring blood concentration of FK506. Frequent measurements should be carried out to decrease renal toxicity induced by FK506. On the other hand, we analyzed the microchimerism in blood and skin of recipients compared with MLR response. Microchimerism dose not seem to be associated with index of MLR response after transplantation. Further study is necessary to confirm this results. For monitoring rejection, HGE of blood was measured in recipients. Blood HGF had a trend to elevate during rejection. We are in progress in investigating the localization of HGF within rejected allografts by immunostaining. Less