Analysis for the mechanism of graft coronary arteriosclerosis

我们开发了长期接受大鼠心脏移植诱导短期治疗FK 506在MHC抗原错配和非MHC，次要抗原错配组合。移植物冠状动脉粥样硬化（GCAS）发生于移植后40天。尽管FK 506治疗，体外细胞活性分析受体脾T细胞在移植后早期在MHC和非MHC错配组合中被识别。在整个观察时间内，在某些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，抗供体抗体不是GCAS诱导所必需的。我们研究了在这个建立的GCAS模型中，通过将同种异体移植物再次移植回原始供体品系来诱导GCAS是否需要持续的同种异体刺激。我们称这种技术为回植。为了确定GCAS变化变得不可逆的时间点，在第3、5、7或9天取出移植的心脏，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天检查这些再次移植的移植物以评估GCAS的等级。如果移植物在首次移植后在第一个受体体内停留长达5天，则将心脏同种异体移植物重新移植回原始供体品系并不能预防GCAS。总之，回植技术显示移植物冠状动脉硬化是在移植后3 - 5天诱导的，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.