Date: Tuesday, May 5, 2015
Session Time: 2:15pm-3:45pm
Presentation Time: 2:39pm-2:51pm
Location: Room 118-C
We have demonstrated that thymus plays an important role in transplantation tolerance in MHC inbred large animals. We have established a technique of isolated vascularized thymic lobe transplantation (VTL) that allows us to study thymic dependent tolerance without changes in thymic structure due to ischemia following thymic transplantation. Utilizing this technique, we have reported VTL-induced transplant tolerance across allogeneic barriers in miniature swine. In this study, we investigated the mechanisms of thymic dependent tolerance utilizing the VTL technique.
MATERIALS and METHODS: MGH MHC-inbred swine were used and allogeneic tolerance was assessed across a class I mismatched barrier using (1) donor-antigen presenting thymii (Donor Ag-VTL) and (2) donor thymic dendritic cells presenting thymii (Donor DC-VTL). Donor Ag-VTL were prepared by exposure to donor antigens in long-term tolerant recipients of class I mismatched kidneys. Donor DC-VTL were prepared by tolerizing recipients to a class I-mismatched thymic graft and then transferring the graft to a thymus-matched recipient, such that the allo VTL contained donor DCs at the corticomedular junction but all of the epithelial cells were recipient-type. Donor Ag-VTLs (Group 1. n=3) or Donor DC-VTLs (Group 2. n=3) were transplanted across class I mismatched barriers with 28 days of FK506; donor type kidneys were transplanted 3 months later without immunosuppression to test for tolerance.
RESULTS: All six recipients in both Groups 1 and 2 showed donor-specific unresponsiveness by in vitro CML assay. However, a striking difference was seen following donor-type kidney transplantation without immunosuppression. All recipients of Donor Ag-VTLs rejected donor MHC matched kidneys at day 7, 8 or 9. In contrast, no graft loss was observed in the recipients of donor DC-VTLs (>200, >70 and >19 days as of the time of this writing). In addition, the results of CD25 depleted CML assays suggested that CD8 T cells were deleted by donor thymic DCs.
CONCLUSIONS: The presence of donor DCs likely plays an essential role in the induction of tolerance in this model. To our knowledge, this is the first report to indicate that donor DCs induced tolerance of kidneys without immunosuppression in a large animal.
To cite this abstract in AMA style:Yamada K, Sekijima M, Kawai A, Tanabe T, Tasaki M, Villani V, Hanekamp I, Shimizu A, Sachs D. Chimeric Thymus Versus Antigen Presenting Thymus for the Induction of Tolerance: Donor DCs in Vascularized Thymus Grafts Play an Essential Role in the Induction of Tolerance [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/chimeric-thymus-versus-antigen-presenting-thymus-for-the-induction-of-tolerance-donor-dcs-in-vascularized-thymus-grafts-play-an-essential-role-in-the-induction-of-tolerance/. Accessed September 23, 2021.
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