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Mechanisms of Alloimmune Tolerance Associated With Mixed Chimerism Induced by Vascularized Bone Marrow Transplants

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Rat limb allograft recipients represent surgically induced, immediately vascularized bone marrow transplant (VBMT) chimeras. The majority of these chimeras undergo tolerance while a minority develop graft versus host disease (GVHD). T-cell chimerism and associated mechanisms of cellular immune nonresponsiveness were investigated in tolerant VBMT chimeras. A strong correlation (p < 0.01) was observed between the clinical onset of GVHD and levels of donor T-cell chimerism approximating or greater than 50%. However, stable mixed chimerism was associated with tolerance. In conclusion, three major sequential mechanisms of immune nonresponsiveness were elucidated in tolerant VBMT chimeras over time and included development of nonspecific suppressor cells (which potentially represent natural suppressor cells), maturation of antigen-specific suppressor cell circuits, and eventually putative clonal inactivation.

Keywords: Key words: Extremity transplant; Composite tissue

Document Type: Research Article


Affiliations: 1: *University of California Davis Medical Center, Division of Surgical & Transplant Pathology, Sacramento, CA 95817 2: †University of Pittsburgh, Department of Surgery, Pittsburgh, PA 15621 3: ‡Cooper Hospital/University Medical Center, UMDNJ-Robert Wood Johnson Medical School, Division of Surgical Research, Camden, NJ, 08103 4: §University of California, Department of Surgery, Irvine, CA 92717 5: ¶CryoLife, Inc., Department of Research and Development, 1655 Roberts Boulevard, Kennesaw, GA 30144

Publication date: 2002-01-01

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  • Cell Transplantation publishes original, peer-reviewed research and review articles on the subject of cell transplantation and its application to human diseases. To ensure high-quality contributions from all areas of transplantation, separate section editors and editorial boards have been established. Articles deal with a wide range of topics including physiological, medical, preclinical, tissue engineering, and device-oriented aspects of transplantation of nervous system, endocrine, growth factor-secreting, bone marrow, epithelial, endothelial, and genetically engineered cells, among others. Basic clinical studies and immunological research papers are also featured. To provide complete coverage of this revolutionary field, Cell Transplantation will report on relevant technological advances, and ethical and regulatory considerations of cell transplants. Cell Transplantation is now an Open Access journal starting with volume 18 in 2009, and therefore there will be an inexpensive publication charge, which is dependent on the number of pages, in addition to the charge for color figures. This will allow work to be disseminated to a wider audience and also entitle the corresponding author to a free PDF, as well as prepublication of an unedited version of the manuscript.
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