TRANSPLANT TOLERANCE IN NONHUMAN PRIMATES

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 为了维持他们的同种异体移植物，患者必须严格遵守使用昂贵的免疫抑制剂的终身治疗方案，这大大增加了心血管疾病，感染和恶性肿瘤的风险。 发展促进接受同种异体组织而不需要铬免疫抑制的策略不仅可以降低这些危及生命的并发症的风险，而且还可以大大扩展器官、组织和细胞移植在血红蛋白病和遗传异常、I型糖尿病以及可能的其他自身免疫性疾病等疾病中的应用。 我们在国内进行了第一例恒河猴供体和受体之间的骨髓移植，这些供体和受体具有已知的家族关系和MHC相似性。 我们的数据表明，在移植供体和受体之间的MHC匹配增加的情况下，基于共刺激阻断的持久嵌合体诱导是可以实现的，但即使在完全MHC匹配的情况下，排斥反应仍然会发生。 此外，我们继续努力确定恒河猴的家族相关性程度和MHC匹配程度。 这项分析从根本上改变了在恒河猴模型中进行和分析造血干细胞移植的方式，并首次允许在已知遗传和MHC差异的供体和受体之间进行移植。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. To maintain their allografts, patients must rigidly adhere to life-long treatment regimens using costly immunosuppressive agents that dramatically increase the risks of cardiovascular disease, infections and malignancies. The development of strategies to promote the acceptance of allogeneic tissues without the need for chromic immunosupression could not only reduce the risk of these life-threatening complications, but also greatly expand the application of organ, tissue and cellular transplantation for diseases such as the hemoglobinopathies and genetic abnormalities, Type I diabetes, and possibly other autoimmune diseases. We performed the first bone marrow transplants in the country between rhesus macaque donors and recipients with known familial relationships and MHC similarity. Our data suggests that in the setting of increased MHC matching between transplant donors and recipients, costimulation blockade-based induction of durable chimerism can be achievable, but that rejection still occurs, even in the setting of full MHC matching. Additionally, we continued to lead an effort to determine the degree of family relatedness and the degree of 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 known genetic and MHC disparity for the first time.