Prope Tolerance to Heart Allografts in Mice Associated With Persistence of Donor Interleukin-10-Transduced Stem Cells

[摘要]：Background. We previously reported that transduction of the human interleukin (IL)-10 gene into the total fetal liver stem cells (hIL-10-TFLs) of mice protects against their rejection in an allogeneic host. In this study, we explored the effects of these cells in two different models of organ transplantation. Methods. Balb/c mice were sublethally irradiated before receiving skin or vascularized heterotopic heart grafts from C57Bl/6 mice. TFLs from C57Bl/6 mice transduced with hIL-10 or untransduced TFLs were injected on the day of transplantation into recipient mice once or also every 20 days thereafter. Results. Skin allograft survival was prolonged for up to 17.8 +/- 0.6 days, vs. 9.0 +/- 0.4 days, in mice that received hIL-10-TFLs or untransduced TFLs, respectively. Allogeneic heart transplants survived for 86.25 +/- 13.8, 46.3 +/- 4.6, 28.1 +/- 6.1, or 11.5 +/- 0.6 days in mice that received repeated injections of hIL-10-TFLs, a single injection of hIL-10-TFLs, repeated injections of untransduced TFLs, or controls, respectively. Histological analyses of the grafts showed fewer inflammatory foci and CD8+ infiltrating cells in mice injected with hIL-10-TFLs compared with untreated mice. Expressions of H-2b and hIL-10 were found in several organs, including the thymus, liver, and the transplant, in hIL-10-TFL-injected mice. Finally, in hIL-10-TFL-injected mice, FoxP3(+) T cells were present inside the transplanted heart as late as 140 days after transplantation. Conclusions. In this study, we showed that repeated injections of hIL-10-TFLs are efficient in mitigating transplant rejection. This "prope" tolerance was associated with survival of donor hematopoietic cells in the host.

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