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

引言。环磷酰胺诱导的小鼠耐受系统主要由供体脾细胞（SC）注射，随后CP处理组成，被发现可用于诱导对各种实体器官的持久同种异体耐受。本研究旨在探讨CP诱导耐受系统诱导的小鼠移植后冠状动脉病变（PTCAD）的发生，并评价耐受程度对预防PTCAD的作用。为了建立一个可重复的PTCAD模型，我们在MHC匹配但H抗原不匹配的供者 * 受体AKR（H-2<@D14@>D1，Thy1.1，Mis-1<@D12@>D1）* C3 H（H-2<@D14@>D1，Thy1.2，Mis-1<@D16@>D1）之间交换异位心脏移植物。Recipeint C3 H小鼠在第0天用1 × 10 <@D18@>D1 SC处理，在第2天用200或100 mg/kg CP处理。心脏移植后，触诊和取出病理研究。结果.在这种组合中，AKR心脏移植（HG）到未移植的C3 H小鼠中存活超过100天，但最终被排斥 ...更多信息 移植后150-250天。在这些移植超过100天后的HG中，组织学分析显示PTCAD的证据（第200天的冠状动脉狭窄率; 68.0（± SD））。间质及血管周围纤维化评分16.0%，平均3.67（±）SY. [）0.58）。在SC/200 mg/kg CP处理的C3 H小鼠中诱导了对AKR皮肤的永久皮肤耐受性，但在SC/100 mg/kg CP处理的C3 H小鼠中未诱导。在两组中均观察到外周中Mils反应性V β 6 <@D1 +@> D1 CD 4 <@D1+@>D1 T细胞的破坏，但在SC/100 mg/kg CP处理的C3 H小鼠中未诱导永久性混合嵌合体。在两组中，AKR HG存活超过300天（n=1.5），内膜增生和血管纤维化均明显有限。讨论和结论。目前的研究表明CP诱导的耐受对PTCAD的有益作用。此外，我们的结果表明，在小鼠心脏移植模型中，诱导永久性皮肤移植物相容性和/或混合嵌合体的深度耐受并不是预防PTCAD所必需的。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