Study of Renal Transplantation by a New Immunosuppressive Method

通过转移化学修饰的同种异体抗原诱导耐受性是去年报道的。为了分析这一机制，我们通过RT-PCR检测了同种异体移植肾耐受模型中的t细胞相关细胞因子。在同种移植物中未观察到mrna细胞因子的表达。相比之下，同种异体移植物表现出Th1 （IL-2, γ - inf）和Th2 （IL-4, IL-10）相关细胞因子mrna的表达。此外，与未处理同种异体移植物相比，处理过的同种异体移植物中IL-2 mRNA的表达较低。这一结果表明，诱导耐受可能是同种异体移植物中Th1/Th2功能免疫重定向的原因。最近，一种新的免疫抑制剂FTY720被开发出来。我们研究了FTY720的免疫抑制作用及其机制。大鼠外周血淋巴细胞明显减少，其他白细胞无明显变化。口服FTY720可提高同种异体移植肾的存活率。更有趣的是，FTY720预处理比移植后给药更有效。长期存活大鼠经FTY720治疗后，脾脏出现萎缩，并进行了细胞凋亡检测。fty720处理的移植大鼠脾脏未见凋亡。然后，在排斥反应期间（移植后第5天）检测脾脏中Th1相关细胞因子的产生。采用RT-PCR法检测移植大鼠脾组织中IL-2 mRNA的表达。然而，FTY720移植大鼠脾脏中没有表达该mRNA。我们推测长期生存的大鼠可能需要脾脏的功能改变。在临床研究中，对接受FK506治疗的患者进行了肾移植的连续活检和FK506的药代动力学研究。我们强调监测FK506血药浓度的重要性。应经常测量以减少FK506引起的肾毒性。另一方面，我们分析了受体血液和皮肤中的微嵌合反应与MLR反应的比较。微嵌合似乎与移植后MLR反应指数无关。需要进一步的研究来证实这一结果。为监测排斥反应，测定受者血液中的HGE。排斥反应时血液HGF有升高的趋势。我们正在通过免疫染色研究排斥同种异体移植物中HGF的定位。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