Abstract
Background: Multilineage chimerism is a promising strategy to induce donor-specific tolerance. Because the beneficial effect of splenic grafting on tolerance induction is well known, we studied long-term hematopoietic chimerism and the fate of donor-derived cells after allogenic pancreas/spleen transplantation. Methods: Green fluorescent protein (GFP) transgenic (Tg) Wistar rats were donors and combined pancreas/spleen transplantation (PST) or pancreas transplantation (PT) alone was performed on recipient LEW rats. Graft survival was compared between these two groups and the fate of donor-derived GFP + cells was analyzed by flow cytometry. In this system, the donor-derived cells were clearly defined as having lymphocytic or granulocytic lineage by cell size. T-cell subsets of GFP + and GFP − cells in long graft-surviving rats were also characterized. Results: The survival period of the grafted pancreas in PST rats was significantly longer than that of PT rats ( P<0.001). Three of seven PST rats survived >250 days. The chimeric level of donor-derived GFP + cells in the recipient peripheral blood was markedly higher in PST rats. In rats with long-surviving grafts, overall peripheral blood chimerism was more than 5%, and both lymphocytes and granulocytes generated from the grafted spleen were stable. T-cell subsets in the recipient LEW rats varied according to the type of cells. CD4 +CD8 + subsets decreased in the GFP + cells and CD4 −CD8 + subsets increased in the GFP − (LEW) cells. Conclusion: We confirmed the combination effect of the grafted spleen on pancreatic graft survival. Donor lymphocytic and granulocytic lineages were generated in the recipients with long-surviving graft. It suggested that multilineage chimerism was often induced by the spleen graft and protected the pancreatic graft against rejection for a long period.
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