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DOI: 10.1177/1522162802005002007 © 2002 SAGE Publications The Use of Allopeptides in Tolerance Induction in Rodents
The development of new approaches to the induction of transplant tolerance has remained the Holy Grail in the field of organ transplantation. The following summarizes the use of MHC allopeptides in the induction of tolerance to various cellular and solid organ allografts in a fully MHC mismatched model. Initial studies using host myeloid dendritic cells, primed with donor allopeptides injected intrathymically or intravenously, led to indefinite cardiac allograft survival. Although the intrathymic route of administration is clinically impractical, it has dominated experimental methods of tolerance induction over the last several years. We have presently developed the use of intravenous administration of either dendritic cells primed in vitro or T-cells primed in vivo with donor MHC Class I immunodominant allopeptides, to induce permanent organ allograft acceptance. The mechanism of allogeneic unresponsiveness in this model appears to be highly dependent on the short-term presence of the thymus since ablation of the thymus within the 1st week of grafting abrogates allograft prolongation. Subsequent cell migration studies showed that activated host T-cells recirculate to the thymus, emphasizing the importance of indirect allopresentation in tolerance induction.
Key Words: tolerance • allopeptides • antigen-presenting cells • T-cell homing
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