TOLERANCE TO HEART TRANSPLANTS IN MINIATURE SWINE

100%小型猪肾移植受者可产生耐受性 选择性地与I类不匹配的同种异体移植并接受12天的治疗 环孢素A的围手术期疗程。世界各地的心脏移植 相同的MHC屏障被相同的处理显著延长 但所有的移植物最终都会被排斥。因此，我们有 检查了心脏和心脏同时移植的反应 这个班我的肾错配了，并做了令人兴奋的观察 肾脏移植似乎完全保护了 从急性和慢性排斥反应中听到。我们当前的目标是 提出的是确定这种保护现象的依据。 具体地说，我们将：1)确定I类心脏是否不匹配 移植物能够维持由 心肾联合移植；2)确定肾、心脏联合移植 诱导/维持正常胸腺对胸腺的要求 对I类不相合心脏移植的耐受性；3)检查 肾脏来源的细胞群体和/或抗原负责 诱导对I类不匹配心脏移植的耐受性，以及 试图利用肾脏花边中的这种细胞和/或抗原来 耐受诱导；4)移植体外参数比较 同种异体心脏移植动物的免疫耐受 与慢性免疫抑制相比，耐受性诱导延长。这些 研究应该对我们的理解具有理论意义 一期带血管同种异体移植诱导耐受的临床应用 与应用诱导容忍有关的影响 心脏移植的治疗方案。

Tolerance is induced in 100% of miniature swine recipients of renal allografts selectively mismatched for class I and treated with a 12 day course of Cyclosporine A perioperatively. Heart transplants across the same MHC barrier are prolonged significantly by the same treatment regimen, but all grafts are eventually rejected. We have therefore examined the response to simultaneous transplantation of both heart and kidney across this class I mismatch and have made the exciting observation that the kidney transplants appear to provide complete protection of the hears from both acute and chronic rejection. Our goal in the current proposal is to determine the basis of this protective phenomenon. Specifically, we shall: 1) Determine whether class I mismatched heart transplants are capable of maintaining the tolerance established by simultaneous transplantation of kidney and heart; 2) Determine the requirements for an intact thymus in the induction/maintenance of tolerance to class I mismatched heart transplants; 3) Examine which kidney-derived cell populations and/or antigens are responsible for induction of tolerance to class I mismatched heart transplants, and attempt to utilize such cells and/or antigens in lace of the kidney for tolerance induction; and 4) Compare in vitro parameters of transplant immunity/tolerance in animals bearing allogeneic heart transplants prolonged by tolerance induction versus Chronic immunosuppression. These studies should have both theoretical implications for our understanding of tolerance induction by primarily vascularized allografts and practical implications with respect to the application of tolerance-inducing regimens to heart transplantation.