Analysis of immunological mechanism and inhibition of post-transplant coronary artery disease in mice.

Intoroduction。环磷酰胺诱导的小鼠耐受系统主要由供体脾细胞（SC）注射和cp处理组成，可用于诱导对各种实体器官的持久同种异体耐受。在本研究中，我们观察了cp诱导耐受系统诱导小鼠移植后冠状动脉疾病（PTCAD）是否发生，并评价了耐受程度对预防PTCAD的作用。为了建立可重复的PTCAD模型，我们在mhc匹配但H抗原不匹配的供体与受体之间交换了AKR (H-2<@D14@>D1, Thy1.1, mis1 <@D12@>D1) *C3H （H-2<@D14@>D1, Thy1.2, mis1 <@D16@>D1）的异体心脏移植物。受体C3H小鼠于第0天给予1x10<@D18@>D1 SC，第2天给予200或100mg/kg CP。对心脏移植物进行触诊并取下进行病理观察。结果。在这种组合中，AKR心脏移植物（HG）在未处理的C3H小鼠中存活超过100天，但最终在移植后150-250天出现排斥反应。移植后100天以上的HG，组织学分析显示PTCAD(第200天冠状动脉狭窄率68.0([SY.+-]])16.0%，间质和血管间质纤维化评分；3.67 [] [.] [.] [.]SC/200mg/kg cp处理的C3H小鼠可诱导对AKR皮肤的永久皮肤耐受，而SC/100mg/kg cp处理的C3H小鼠则不能。在两组中均观察到外周Milsreactive Vbeta6<@D1+@>D1CD4<@D1+@>D1 T细胞的破坏，但SC/100mg/kg cp处理的C3H小鼠未诱导永久性混合嵌合。两组中，AKR HG存活时间均超过300天（n=1.5），内膜增生和血管纤维化均明显受限。讨论与结论。目前的研究表明，cp诱导的耐受性对PTCAD有有益的作用。此外，我们的研究结果表明，在小鼠心脏移植模型中，诱导永久性皮肤移植接受和/或混合嵌合的高度耐受性并不需要预防PTCAD。少

Intoroduction. A cyclophosphamide-induced tolerance system in mice that primarily consists of donor spleen cells (SC) injection fellowed by CP-treatment was found useful for inducing a long-lasting allo-tolerance to various solid organs. In the present study, we investigated whether post-transplant coronary disease (PTCAD) occurs in mice induced by CP-induced tolerance system, and evaluated the degree of tolerance to prevent PTCAD.Methods. To develop a reproducible model of PTCAD,we exchaged heterotopic cardiac allografts between MHC-matched but minor H antigen-mismatched donor*recipient comvination of AKR (H-2<@D14@>D1, Thy1.1, Mis-1<@D12@>D1) *C3H (H-2<@D14@>D1, Thy1.2, Mis-1<@D16@>D1). Recipeint C3H mice were treated with 1x10<@D18@>D1 SC on day 0 and 200 or 100mg/kg CP on day 2. The cardiac grafts were followed by palpation and removed for pathologic study. Result. In this combination, AKR heart grafts (HG) into untrreated C3H mice survived over 100 days, but were finally rejected … More 150-250 days after transplant. In these HG after over 100 days of transplant, histological analysis showed the evidence of PTCAD (coronary artries stenosis ratio on day 200 ; 68.0(]SY.+-。[)16.0%, score of interstitial and pervascular fibrosis ; 3.67(]SY.+-。[)0.58). Permanent skin tolerance to AKR skin was induced in SC/200mg/kg CP-treated C3H mice, but not in SC/100mg/kg CP-treated C3H mice. Destruction of Milsreactive Vbeta6<@D1+@>D1CD4<@D1+@>D1 T cells in the periphery was observed in both groups, but permanent mixed chimerism was not induced in SC/100mg/kg CP-treated C3H mice. In both groups, AKR HG survived for more than 300 days (n=1.5), and both intimal hyperplasia and vascular fibrosis was remarkably limited. Discussion and Conclusion. Present study indicated the beneficial effect of CP-induced tolerance on PTCAD.Furthermore, our results indicated that profound degree of tolerance to induce permanent skin graft acceotance and/or mixed chimerism was not required to prevent PTCAD in murine heart transplant model. Less