Girlanda Raffaele, Kirk Allan D
Transplantation Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
J Am Soc Nephrol. 2007 Aug;18(8):2242-51. doi: 10.1681/ASN.2007020180. Epub 2007 Jul 18.
Vascularized allografts are rejected unless some indefinite modification to the recipient's immune system is made. This modification is typically achieved through the long-term administration of immunosuppressive drugs. Patients thus trade their end-stage organ failure for dependence on daily drug therapy and the accompanying chronic condition of immunodeficiency. However, it is clear from studies in experimental animals that rejection can be prevented through the use of several therapeutic approaches, including donor hematopoietic cell infusion, chimerism, T cell depletion, and/or co-stimulation blockade. Successfully treated animals avoid rejection beyond the period of therapy without a phenotype of chronic immunosuppression and are thus considered to be tolerant of their grafts. Although intriguing, this success in animals has yet to be reproducibly translated to the clinic, and human transplant recipients remain tethered to immunosuppressive drugs with rare exceptions. This article provides an overview of the existing, largely anecdotal, clinical experience with organ allograft tolerance. It reviews the various approaches that are being applied in pilot human trials and suggests avenues for future clinical investigation.
除非对受体的免疫系统进行某种不确定的修饰，否则血管化同种异体移植物会被排斥。这种修饰通常通过长期服用免疫抑制药物来实现。因此，患者用终末期器官衰竭换取了对每日药物治疗的依赖以及随之而来的慢性免疫缺陷状态。然而，从实验动物研究中可以清楚地看到，通过使用几种治疗方法可以预防排斥反应，包括供体造血细胞输注、嵌合体形成、T细胞清除和/或共刺激阻断。成功治疗的动物在治疗期过后避免了排斥反应，且没有慢性免疫抑制的表型，因此被认为对其移植物具有耐受性。尽管很有趣，但动物实验的这一成功尚未在临床上得到可重复的验证，人类移植受者除了极少数例外，仍然依赖免疫抑制药物。本文概述了现有的、大多为轶事性的器官同种异体移植耐受性临床经验。它回顾了正在进行的人体试验中应用的各种方法，并提出了未来临床研究的途径。
