Adoptive Transfer of Renal Allograft Tolerance in a Large Animal Model |
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Authors: | V Villani K Yamada J R Scalea B C Gillon J S Arn M Sekijima M Tasaki T A Cormack S G Moran R Torabi A Shimizu D H Sachs |
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Institution: | Transplantation Biology Research Center (TBRC) Laboratories, Center for Transplantation Sciences (CTS), Massachusetts General Hospital, Harvard Medical School, Boston, MA |
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Abstract: | Our recent studies in an inbred swine model demonstrated that both peripheral and intra‐graft regulatory cells were required for the adoptive transfer of tolerance to a second, naïve donor‐matched kidney. Here, we have asked whether both peripheral and intra‐graft regulatory elements are required for adoptive transfer of tolerance when only a long‐term tolerant (LTT) kidney is transplanted. Nine highly‐inbred swine underwent a tolerance‐inducing regimen to prepare LTT kidney grafts which were then transplanted to histocompatible recipients, with or without the peripheral cell populations required for adoptive transfer of tolerance to a naïve kidney. In contrast to our previous studies, tolerance of the LTT kidney transplants alone was achieved without transfer of additional peripheral cells and without strategies to increase the number/potency of regulatory T cells in the donor. This tolerance was systemic, since most subsequent, donor‐matched challenge kidney grafts were accepted. These results confirm the presence of a potent tolerance‐inducing and/or tolerance‐maintaining cell population within LTT renal allografts. They suggest further that additional peripheral tolerance mechanisms, required for adoptive transfer of tolerance to a naïve donor‐matched kidney, depend on peripheral cells that, if not transferred with the LTT kidney, require time to develop in the adoptive host. |
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Keywords: | Kidney (allograft) function/dysfunction tolerance: experimental |
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