TOLERANCE TO HEART TRANSPLANTS IN MINIATURE SWINE

小型猪对心脏移植的耐受性

• 批准号: 6445532
• 负责人: DAVID H SACHS
• 金额: $ 20.59万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-03-01 至 2002-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6445532
• 关键词: MHC class I antigen; artificial immunosuppression; cyclosporines; heart transplantation; histocompatibility; histopathology; homologous transplantation; immune tolerance /unresponsiveness; immunosuppressive; kidney transplantation; miniature swine; nonhuman therapy evaluation; thymectomy; thymus; tissue /cell culture; transplant rejection; transplantation immunology

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.

在100%的小型猪肾移植受体中诱导了耐受性。 I类选择性不匹配的同种异体移植物， 围手术期环孢素A疗程。心脏移植手术 相同的MHC屏障被相同的治疗显著延长 但所有移植物最终都被排斥。我们因此 检查了对心脏和心脏同时移植的反应， 我发现了一个令人兴奋的发现， 肾脏移植似乎可以完全保护 急性和慢性排斥反应都有。我们在当前的目标 建议是确定这种保护现象的基础。 具体而言，我们应：1）确定I类错配心脏是否 移植物能够维持由以下因素建立的耐受性： 肾心联合移植; 2）确定 诱导/维持中对完整胸腺的要求 对I类不匹配心脏移植的耐受性; 3）检查 肾来源的细胞群和/或抗原负责 诱导对I类错配心脏移植的耐受，和 试图在肾脏的组织中利用这些细胞和/或抗原， 耐受诱导;和4）比较移植物的体外参数 同种异体心脏移植动物的免疫/耐受 通过耐受诱导与慢性免疫抑制延长。这些 研究应该对我们理解 主要血管化同种异体移植物的耐受诱导和实用 关于应用诱导耐受的 心脏移植的治疗方案