George J F, Goldstein D R, Thomas J M
Department of Surgery, Division of Cardiothoracic Surgery, University of Alabama at Birmingham, Birmingham, AL 35294-0007, USA.
Int J Mol Med. 1999 Nov;4(5):475-82. doi: 10.3892/ijmm.4.5.475.
The induction of transplantation tolerance, defined as the indefinite existence of an intact, functioning allograft, has been a goal of transplantation immunologists for decades because of the morbid effects of immunosuppressive drugs required to maintain graft function. One promising method of tolerance induction involves the peritransplant administration of cytoablative drugs followed by administration of a low dose of donor bone marrow cells. A subpopulation of donor bone marrow cells bearing the CD8 accessory molecule cause the functional deletion of graft reactive T cells via a CD95 dependent mechanism that also involves the cytokine TGFbeta. This interaction is bi-directional in which the bone marrow cell deletes the graft reactive T cell that recognizes it. Therefore, only T cells that recognize the donor antigens are deleted, leaving the immune response to other antigens intact. This protocol has been successfully used in rodents and an outbred large animal model. Clinical trials of donor bone marrow administration are now underway and initially indicate that administration of donor bone marrow is clinically safe.
移植耐受的诱导，定义为完整、功能正常的同种异体移植物的无限期存活，几十年来一直是移植免疫学家的目标，因为维持移植物功能所需的免疫抑制药物具有不良影响。一种有前景的耐受诱导方法包括在移植前后给予细胞消融药物，随后给予低剂量的供体骨髓细胞。携带CD8辅助分子的供体骨髓细胞亚群通过一种依赖CD95的机制导致移植物反应性T细胞的功能缺失，该机制还涉及细胞因子转化生长因子β（TGFβ）。这种相互作用是双向的，即骨髓细胞会删除识别它的移植物反应性T细胞。因此，只有识别供体抗原的T细胞被删除，对其他抗原的免疫反应保持完整。该方案已在啮齿动物和远交系大型动物模型中成功应用。目前正在进行供体骨髓给药的临床试验，初步结果表明供体骨髓给药在临床上是安全的。
