Analysis for the mechanism of graft coronary arteriosclerosis

我们在MHC抗原错配和非MHC、次要抗原错配组合中，通过短期治疗FK506诱导大鼠心脏同种异体移植物的长期接受。移植后第40天，移植冠状动脉粥样硬化（GCAS）发生明确改变。尽管接受了FK506治疗，但在MHC和非MHC错配组合的移植后早期，受体脾脏T细胞的体外细胞活性都得到了识别。在部分MHC错配组合病例中检测到抗供体抗体，但在整个观察时间内未检测到非MHC错配组合病例。这些数据提示抗供体抗体不是诱导GCAS所必需的。在建立的GCAS模型中，我们通过将同种异体移植物重新移植回原供体株来检验是否需要持续的同种异体刺激来诱导GCAS。我们称这种技术为器官移植。为了确定GCAS变化变得不可逆的时间点，在第3天、第5天、第7天或第9天取出移植心脏，并重新移植到供体大鼠中，以防止进一步的免疫刺激。第40天对这些再移植的移植物进行GCAS评分。如果首次移植后同种异体心脏移植物在第一个受体体内停留长达5天，则将移植物重新移植回原供体株并不能预防GCAS。总之，返回移植技术显示移植后3 - 5天发生了冠状动脉硬化，并且没有后续的异源刺激。

We developed long-term acceptance of rat heart allografts induced by short-course treatment of FK506 in both MHC antigen mismatch and non-MHC,minor antigen mismatch combinations. Graft coronary arteriosclerosis (GCAS) was occurred in these long surviving grafts Definite GCAS change was clarified on day 40 after transplantation. In spite of FK506 treatment, in vitro cellular activities analyzed recipient spleen T cells were recognized in early phase of posttransplantation in both MHC and non-MHC mismatch combinations. Anti-donor antibodies were detected in some cases of MHC mismatch combination, but not in any cases of non-MHC mismatch combination throughout the observation time. These data suggest that anti-donor antibody is not essential for GCAS induction. We examined that whether continuous allostimulation was necessary for GCAS induction by retransplantation of allografts back into the original donor strain in this established GCAS model. We call this technique return transplantation. To ascertain the point at which the GCAS changes become irreversible, the grafted hearts were removed on day 3,5,7, or 9, and retransplanted into the donor strain rats to prevent further immunological stimulation. These retransplanted grafts were examined to evaluate the grade of GCAS on day 40. Retransplanted heart allografts back into the original donor strain did not prevent GCAS if the graft had resided in the first recipient for up to 5 days after first transplantation. In conclusion, return transplantation technique revealed that graft coronary arteriosclerosis was induced between 3 and 5 days posttransplantation and develop without subsequent allostimulation.