Tolerance, mixed chimerism and protection against graft-versus-host disease after total lymphoid irradiation

Total lymphoid irradiation (TLI), originally developed as a non-myeloablative treatment for Hodgkin's disease, has been adapted for the induction of immune tolerance to organ allografts in rodents, dogs and non-human primates. Moreover, pretransplantation TLI has been used in prospective studie...

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Bibliographic Details
Published in:Philosophical transactions of the Royal Society of London. Series B. Biological sciences 2001-05, Vol.356 (1409), p.739-748
Main Authors: Field, Elizabeth H., Strober, Samuel
Format: Article
Language:English
Subjects:
Animals
Blood
Bone Marrow Transplantation - immunology
Chimerism
Cytokines - secretion
Graft rejection
Graft vs host disease
Graft vs Host Disease - prevention & control
Graft-Versus-Host Disease
Homologous transplantation
Humans
Immune tolerance
Lymphatic irradiation
Lymphatic Irradiation - methods
Natural Killer T Cells
Organ Transplantation
T lymphocytes
T-Lymphocyte Subsets - immunology
Tissue grafting
Tolerance
Total Lymphoid Irradiation
Transplantation
Transplantation Chimera - immunology
Transplantation Tolerance - immunology
Transplantation, Homologous - immunology
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Summary:Total lymphoid irradiation (TLI), originally developed as a non-myeloablative treatment for Hodgkin's disease, has been adapted for the induction of immune tolerance to organ allografts in rodents, dogs and non-human 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 non-chimeric, 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 graft-versus-host 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 post-transplantation TLI regimen has been developed resulting in stable mixed chimerism and tolerance that is enhanced by a brief course of cyclosporine. The post-transplantation 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.
ISSN:0962-8436
1471-2970
DOI:10.1098/rstb.2001.0851