Preclinical studies have shown that persistent mixed chimerism is linked to acceptance of organ allografts without immunosuppressive (IS) drugs. Mixed chimerism refers to continued mixing of donor and recipient hematopoietic cells in recipient tissues after transplantation of donor cells. To determine whether persistent mixed chimerism and tolerance can be established in patients undergoing living donor kidney transplantation, we infused allograft recipients with donor T cells and hematopoietic progenitors after posttransplant lymphoid irradiation. In 24 of 29 fully human leukocyte antigen (HLA)-matched patients who had persistent mixed chimerism for at least 6 months, complete IS drug withdrawal was achieved without subsequent evidence of rejection for at least 2 years. In 10 of 22 HLA haplotype-matched patients with persistent mixed chimerism for at least 12 months, reduction of IS drugs to tacrolimus monotherapy was achieved. Withdrawal of tacrolimus during the second year resulted in loss of detectable chimerism and subsequent rejection episodes, unless tacrolimus therapy was reinstituted. Posttransplant immune reconstitution of naïve B cells and B cell precursors was more rapid than the reconstitution of naïve T cells and thymic T cell precursors. Robust chimerism was observed only among naïve T and B cells but not among memory T cells. No evidence of rejection was observed in all surveillance graft biopsies obtained from mixed chimeric patients withdrawn from IS drugs, and none developed graft-versus-host disease. In conclusion, persistent mixed chimerism established in fully HLA- or haplotype-matched patients allowed for complete or partial IS drug withdrawal without rejection.

中文翻译：

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混合抑制和免疫抑制药物撤药后接受肾移植。

临床前研究表明，持续混合嵌合体与不接受免疫抑制（IS）药物的器官同种异体移植的接受程度有关。混合嵌合是指供体细胞移植后供体和受体造血细胞在受体组织中的持续混合。为了确定在进行活体供体肾脏移植的患者中是否可以建立持久的混合嵌合和耐受性，我们在移植后的淋巴样照射后向同种异体移植受体中注入了供体T细胞和造血祖细胞。在29例持续混合嵌合至少6个月的完全人类白细胞抗原（HLA）匹配患者中，有24例实现了完全IS药物戒断，而没有随后至少2年的排斥反应证据。在22例HLA单体型匹配的患者中，至少有12个月持续混合嵌合，将IS药物减少至他克莫司单药治疗。除非重新开始他克莫司治疗，否则第二年他克莫司的退出会导致可检测的嵌合体丧失和随后的排斥反应。原始B细胞和B细胞前体的移植后免疫重建比原始T细胞和胸腺T细胞前体的重建更快。健壮的嵌合体仅在幼稚的T和B细胞中观察到，而在记忆T细胞中则未观察到。在所有从IS药物中退出的混合嵌合患者中获得的所有监测移植活检中均未观察到排斥反应的证据，也没有发生移植物抗宿主病的情况。结论，