Journal article
Tolerance, mixed chimerism and protection against graft-versus-host disease after total lymphoid irradiation
Philosophical transactions. Biological sciences, Vol.356(1409), pp.739-748
05/29/2001
DOI: 10.1098/rstb.2001.0851
PMCID: PMC1088460
PMID: 11375076
Abstract
Total lymphoid irradiation (TLI), originally developed as a nonmyeloablative treatment for Hodgkin's disease, has been adapted for the induction of immune tolerance to organ allografts in rodents, dogs and nonhuman primates. Moreover, pretransplantation TLI has been used in prospective studies to demonstrate the feasibility of the induction of tolerance to cadaveric kidney allografts in humans. Two types of tolerance, chimeric and nonchimeric, develop after TLI treatment of hosts depending on whether donor bone marrow cells are transplanted along with the organ allograft. An advantageous feature of TLI for combined marrow and organ transplantation is the protection against graftversushost disease (GVHD) and facilitation of chimerism afforded by the predominance of CD4NK1.1like T cells in the irradiated host lymphoid tissues. Recently, a completely posttransplantation TLI regimen has been developed resulting in stable mixed chimerism and tolerance that is enhanced by a brief course of cyclosporine. The posttransplantation protocol is suitable for clinical cadaveric kidney transplantation. This review summarizes the evolution of TLI protocols for eventual application to human clinical transplantation and discusses the mechanisms involved in the induction of mixed chimerism and protection from GVHD.
Total lymphoid irradiation (TLI), originally developed as a nonmyeloablative treatment for Hodgkin's disease, has been adapted for the induction of immune tolerance to organ allografts in rodents, dogs and nonhuman primates. Moreover, pretransplantation TLI has been used in prospective studies to demonstrate the feasibility of the induction of tolerance to cadaveric kidney allografts in humans. Two types of tolerance, chimeric and nonchimeric, develop after TLI treatment of hosts depending on whether donor bone marrow cells are transplanted along with the organ allograft. An advantageous feature of TLI for combined marrow and organ transplantation is the protection against graftversushost disease (GVHD) and facilitation of chimerism afforded by the predominance of CD4 NK1.1 like T cells in the irradiated host lymphoid tissues. Recently, a completely posttransplantation TLI regimen has been developed resulting in stable mixed chimerism and tolerance that is enhanced by a brief course of cyclosporine. The posttransplantation protocol is suitable for clinical cadaveric kidney transplantation. This review summarizes the evolution of TLI protocols for eventual application to human clinical transplantation and discusses the mechanisms involved in the induction of mixed chimerism and protection from GVHD.
Details
- Title: Subtitle
- Tolerance, mixed chimerism and protection against graft-versus-host disease after total lymphoid irradiation
- Creators
- Elizabeth H Field - Department of Internal Medicine, University of Iowa College of MedicineSamuel Strober - Division of Rheumatology and Immunology, Department of Medicine, Stanford University School of Medicine
- Resource Type
- Journal article
- Publication Details
- Philosophical transactions. Biological sciences, Vol.356(1409), pp.739-748
- DOI
- 10.1098/rstb.2001.0851
- PMID
- 11375076
- PMCID
- PMC1088460
- NLM abbreviation
- Philos Trans R Soc Lond B Biol Sci
- ISSN
- 0962-8436
- eISSN
- 1471-2970
- Publisher
- The Royal Society
- Language
- English
- Date published
- 05/29/2001
- Academic Unit
- Immunology; Internal Medicine
- Record Identifier
- 9984094514202771
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