TOLERANCE INDUCTION USING DST AND CYCLOSPORINE

众所周知，输血可以产生强大而持久的效果。 免疫抑制效应，既有供体特异的，也有非供体特异的。在……里面 实验动物，使用非常严格的ACI to Lewis模型 异位同种异体心脏移植的免疫抑制作用 研究发现，如果只输血24小时，输血量最大。 移植前环孢素同时开始的时间 时间到了。当环孢素以低剂量仅持续30天时，以及 所有免疫抑制停止，供者特异性耐受，烫发- 移植物暂时存活在一些动物身上，但不是所有动物身上。近期 研究表明，更有效地产生永久耐受 可以通过使用单抗进行部分淋巴细胞减少来实现 紧接供者特异性输血前的抗体，并通过给予 在移植后的第一个月内额外输血三次。 这些发现为使用供者特异性 身体肾移植受者的输血。事实上，一个首字母 正在进行的随机前瞻性研究表明，使用身体 移植前24小时的供者特异性输血，以及 静脉注射不含抗淋巴细胞球蛋白的环孢素 在术后前6个月内未发生排斥事件 移植且无排斥反应所致的肾脏损失(9例患者如此治疗 很远)。目前的提议旨在测试额外的模式 单剂抗T细胞淋巴细胞单抗的研究 在供体特异性输血和环孢素诱导前 身体肾的接受者也将接受捐赠者的特定血液 移植后期间的输血或骨髓输注。 由于移植耐受与输血相关是一种积极的 涉及特异性巨噬细胞和T细胞发育的免疫过程 淋巴细胞抑制细胞网络，预计耐受性， 也许与微嵌合体有关，将导致持久的 人类同种异体移植物在很少或没有持续免疫抑制情况下存活。

Blood transfusions are known to exert a powerful and long-lasting immunosuppressive effect which is both donor specific and non-specific. In laboratory animals, using the very stringent ACI to Lewis model of heterotopic cardiac allografts, the immunosuppressive effect of a single blood transfusion has been found to be maximal if it is given only 24 hours before the time of transplantation when cyclosporine is begun at the same time. When cyclosporine is continued at a low dose for only 30 days, and all immunosuppression discontinued, donor specific tolerance, with perm- anent survival of the graft occurs in some but not all animals. Recent studies have shown that a more efficient production of permanent tolerance can be achieved by a partial lymphocyte reduction using a monoclonal antibody immediately before the donor specific transfusion and by giving three additional transfusions during the first month post transplant. These findings provide a solid laboratory basis for using donor specific transfusions in recipients of cadaveric kidneys. Indeed, an initial ongoing randomized prospective study has shown that the use of cadaveric donor specific transfusions 24 hours before transplant, along with intravenous cyclosporine without an anti-lymphocyte globulin, has resulted in no occurrence of rejection episodes within the first six months post transplant and no loss of kidneys from rejection (9 patients treated so far). The current proposal is designed to test the additional modalities of a single dose of an anti T cell lymphocyte monoclonal antibody immediately before donor specific transfusion and cyclosporine induction in recipients of cadaveric kidneys who will also receive donor specific blood transfusions or bone marrow transfusions during the post transplant period. Since graft tolerance associated with administration of blood is an active immunologic process involving the development of specific macrophage and T lymphocyte suppressor cell networks, it is anticipated that tolerance, perhaps in association with microchimerism, will result in long-lasting allograft survival with little or no continued immunosuppression in man.