Analysis for the mechanism of graft coronary arteriosclerosis

我们开发了对 MHC 抗原错配和非 MHC、次要抗原错配组合中 FK506 短期治疗诱导的大鼠同种异体心脏移植的长期接受度。这些长期存活的移植物中发生了移植物冠状动脉硬化(GCAS)。移植后第40天明确了GCAS变化。尽管进行了 FK506 治疗，但在移植后早期阶段，在 MHC 和非 MHC 错配组合中均识别出受者脾脏 T 细胞的体外细胞活性分析。在整个观察时间内，在一些 MHC 错配组合病例中检测到抗供体抗体，但在任何非 MHC 错配组合病例中均未检测到。这些数据表明抗供体抗体对于 GCAS 诱导并不是必需的。我们通过在这个已建立的 GCAS 模型中将同种异体移植物重新移植回原始供体菌株来检查连续同种异体刺激对于 GCAS 诱导是否是必要的。我们称这种技术为回归移植。为了确定 GCAS 变化变得不可逆转的时间点，在第 3、5、7 或 9 天取出移植心脏，并重新移植到供体品系大鼠中，以防止进一步的免疫刺激。在第 40 天检查这些再移植的移植物以评估 GCAS 的等级。如果移植物在第一次移植后在第一个受体体内停留长达 5 天，则将同种异体心脏再移植回原始供体品系并不能预防 GCAS。总之，回程移植技术表明，移植物冠状动脉硬化是在移植后 3 至 5 天之间诱导的，并且在没有随后的同种异体刺激的情况下发展。

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.