TRANSPLANT TOLERANCE IN NONHUMAN PRIMATES

非人类灵长类动物的移植耐受性

• 批准号: 8357393
• 负责人: CHRISTIAN P LARSEN
• 金额: $ 4.12万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357393
• 关键词: Adhesions; Allogenic; Allografting; Autoimmune Diseases; Chimerism; Chronic; Data; Development; Disease; Donor person; Family; Funding; Genetic; Grant; Hematopoietic stem cells; Hemoglobinopathies; Immune Tolerance; Immunologic Deficiency Syndromes; Immunosuppressive Agents; Infection; Insulin-Dependent Diabetes Mellitus; Lead; Life; Macaca mulatta; Malignant Neoplasms; Modeling; Monitor; National Center for Research Resources; Organ; Patients; Primates; Principal Investigator; Research; Research Infrastructure; Resources; Risk; Source; Stem cell transplant; TNFRSF5 gene; Time; Tissues; Transplant Recipients; Transplantation; Treatment Protocols; United States National Institutes of Health; base; cardiovascular disorder risk; cohort; cost; nonhuman primate; prospective; research study

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. To maintain allografts patients must adhere to life-long treatment regimens using costly immunosuppressive agents that dramatically increase the risks of cardiovascular disease, infections and malignancy. The development of strategies to promote the acceptance of allogenic tissues without the need for chronic immunosuppressant could reduce the risk of these complications and greatly expand the application of organ, tissue, and cellular transplantation for diseases such as the hemoglobinopathies and genetic immunodeficiencies, Type 1 diabetes and other autoimmune diseases. We continue to lead an effort to determine the degree of family relatedness and MHC matching in Rhesus Macaques. This analysis has fundamentally changed the way hematopoietic stem cell transplants are performed and analyzed in the Rhesus model, and have allowed transplants between donors and recipients of know genetic and MHC disparity for the first time. Our data suggest that the setting of increased MHC matching between transplant donors and recipients, Costimulation blockade-based induction of durable Chimerism can be achieved. However, rejection still occurs, even with full MHC matching. We have continued experiments with Rhesus transplant pairs with a known degree of relatedness and MHV matching. Our results indicate that the addition of either CD40-directed or LFA-1 directed Costimulation/adhesion blockade can significantly enhance donor Chimerism induction and that in some cases, it is durable. We are continuing our prospective monitoring of Chimerism and immune tolerance in these transplant cohorts.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 为了维持同种异体移植，必须使用昂贵的免疫抑制剂来遵守终身治疗方案，从而大大增加心血管疾病，感染和恶性肿瘤的风险。在不需要慢性免疫抑制剂的情况下促进同种异体组织接受的策略的制定可以降低这些并发症的风险，并大大扩展器官，组织和细胞移植的应用，例如血红蛋白疗法和诸如遗传免疫缺陷的诸​​如1型生物疾病和其他自动性疾病。我们继续努力确定恒河猕猴的家庭相关性和MHC匹配程度。该分析从根本上改变了恒河猴模型中造血干细胞移植和分析的方式，并首次允许供体和知识遗传和MHC差异的受体之间进行移植。我们的数据表明，可以在移植供体和受体之间增加MHC匹配的设置，可以实现基于耐用的嵌合式粘液障碍的诱导。但是，即使有完整的MHC匹配，拒绝仍然会发生。我们继续对具有已知程度的相关性和MHV匹配的恒河体移植对进行实验。我们的结果表明，添加CD40定向或LFA-1的指向共刺激/粘附阻滞可以显着增强供体嵌合感，并且在某些情况下，它是持久的。我们正在继续对这些移植队列中的嵌合和免疫耐受性进行前瞻性监测。