Department of Medicine (Nephrology), Stanford University School of Medicine, Stanford, CA, USA.
Am J Transplant. 2012 May;12(5):1133-45. doi: 10.1111/j.1600-6143.2012.03992.x. Epub 2012 Mar 8.
Sixteen patients conditioned with total lymphoid irradiation (TLI) and antithymocyte globulin (ATG) were given kidney transplants and an injection of CD34+ hematopoietic progenitor cells and T cells from HLA-matched donors in a tolerance induction protocol. Blood cell monitoring included changes in chimerism, balance of T-cell subsets and responses to donor alloantigens. Fifteen patients developed multilineage chimerism without graft-versus-host disease (GVHD), and eight with chimerism for at least 6 months were withdrawn from antirejection medications for 1-3 years (mean, 28 months) without subsequent rejection episodes. Four chimeric patients have just completed or are in the midst of drug withdrawal, and four patients were not withdrawn due to return of underlying disease or rejection episodes. Blood cells from all patients showed early high ratios of CD4+CD25+ regulatory T cells and NKT cells versus conventional naive CD4+ T cells, and those off drugs showed specific unresponsiveness to donor alloantigens. In conclusion, TLI and ATG promoted the development of persistent chimerism and tolerance in a cohort of patients given kidney transplants and hematopoietic donor cell infusions. All 16 patients had excellent graft function at the last observation point with or without maintenance drugs.
十六例患者接受了全身淋巴照射（TLI）和抗胸腺细胞球蛋白（ATG）预处理，并在诱导耐受方案中接受了 HLA 匹配供者的 CD34+造血祖细胞和 T 细胞移植。血细胞监测包括嵌合体变化、T 细胞亚群平衡和对供者同种异体抗原的反应。十五例患者在无移植物抗宿主病（GVHD）的情况下发生多系嵌合体，八例嵌合体至少 6 个月的患者停用抗排斥药物 1-3 年（平均 28 个月），随后无排斥发作。四名嵌合体患者刚刚完成或正在进行停药，四名患者因基础疾病复发或排斥发作而未停药。所有患者的血细胞均显示早期 CD4+CD25+调节性 T 细胞和 NKT 细胞与常规幼稚 CD4+T 细胞的高比值，且停药患者对供者同种异体抗原表现出特异性无反应性。总之，TLI 和 ATG 促进了接受肾移植和造血供者细胞输注的患者队列中持续性嵌合体和耐受的发展。在最后一次观察时，所有 16 例患者无论是否使用维持药物，均具有良好的移植物功能。
