ACQUIRED TOLERANCE TO CARDIAC XENOGRAFT

虽然临床心脏移植是治疗急性心肌梗死的有效方法 终末期心脏病患者目前供体短缺 器官限制了这种治疗的效果。器官的一种解决方案 供体短缺是指利用动物器官进行人体移植。 (异种移植)。目前，免疫屏障对 异种移植排除了这一可行的替代方案。在以前的 在同种异体移植的动物模型中，免疫耐受 通过将受体动物暴露在同种异体细胞中而产生 或者在免疫系统不成熟的时候(胎儿、新生儿)或者 通过将一过性免疫抑制的成熟动物暴露于抗原 胸腺内。这项研究计划试图将这些观察扩展到 一种使用大鼠供体和小鼠受体的异种移植模型。 由于分子试剂的可用性，这种模型是有利的。 允许在分子水平上研究小鼠的免疫系统。这个 研究计划反映了之前在同种移植模型中的工作。这个 研究将探索暴露未成熟小鼠的不同方法 免疫系统对大鼠细胞的影响以及随后对 带血管的心脏移植。此外，对成年小鼠的前处理 受者之后将暴露于供体细胞，并随后 带血管的异种心脏移植。

Although clinical cardiac transplantation is effective therapy for patients with end stage cardiac disease the current shortage of donor organs limits the efficacy of this treatment. One solution to the organ donor shortage is the use of animal organs for human transplantation (xenotransplantation). Presently the immunologic barrier to xenotransplantation preclude this as a viable alternative. In previous work in an animal model of allo-transplantation, immune tolerance has been produced by exposure of the recipient animal to allogeneic cells either at a time when the immune system is immature (fetal, neonatal) or by exposing a transiently immunosuppressed mature animal to antigen intrathymicaIly. This research plan seeks to extend these observations to a model of xenotransplantation using a rat donor and mouse recipient. This model is advantageous since the availability of molecular reagents allows study of the mouse immune system at the molecular level. The research plan mirrors previous work in the allotransplant model. The research will explore different methods of exposing the immature murine immune system to rat cells and the subsequent response to a vascularizedcardiac graft. In addition, pretreatment of adult murine recipients will be followed by exposure to donor cells and subsequent vascularized cardiac xenotransplantation.