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Frontiers in Nephrology: Immune Tolerance to Allografts in Humans

Transplantation Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland

Correspondence: Dr. Allan D. Kirk, Room 5-5752, Building 10CRC, Center Drive, Bethesda, MD 20892. Phone: 301-496-3047; Fax: 301-451-6989; E-mail: allank{at}intra.niddk.nih.gov

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.

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				P. S. Heeger Frontiers in Nephrology: Tolerance J. Am. Soc. Nephrol., August 1, 2007; 18(8): 2240 - 2241. [Full Text] [PDF]

Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673