We previously induced long-term allograft acceptance in an allogeneic lung transplantation (LTx) model in miniature swine using perioperative non-myeloablative irradiation (IRR) combined with infusion of donor specific alloantigen. In order to improve clinical applicability, we delayed induction with irradiation in this study. Left sided single LTx was performed in minipigs. Group 1 received non-myeloablative irradiation (7Gy thymus and 1.5Gy whole body IRR) before LTx and a perioperative donor specific splenocyte infusion (SpTx). Group 2 received perioperative SpTx but delayed IRR three days after LTx. Group 3 was exposed to delayed IRR without SpTx. Whereas 4 out of 7 animals from the non-delayed group never rejected their grafts and were electively sacrificed on postoperative day (POD) +500, all animals from group 2 rejected their grafts before POD 108. In group 3, 3 out of 8 animals developed long-term allograft acceptance. In all groups, donor leukocyte chimerism peaked up to 20% in peripheral blood one hour after reperfusion of the lung. Group 1 maintained prolonged chimerism beyond POD 7, whereas chimerism levels in groups 2 and 3 decreased continuously thereafter. Delayed irradiation has the potential to improve long-term graft survival, yet not as efficient as a perioperative conditioning protocol.

我们之前使用围手术期非清髓性照射 (IRR) 结合供体特异性同种异体抗原的输注，在小型猪的同种异体肺移植 (LTx) 模型中诱导了长期同种异体移植物接受。为了提高临床适用性，我们在本研究中延迟了照射诱导。在小型猪中进行左侧单次 LTx。第 1 组在 LTx 和围手术期供体特异性脾细胞输注 (SpTx) 之前接受了非清髓性照射（7Gy 胸腺和 1.5Gy 全身 IRR）。第 2 组接受围手术期 SpTx，但在 LTx 后三天延迟 IRR。第 3 组暴露于没有 SpTx 的延迟 IRR。而来自非延迟组的 7 只动物中有 4 只从未拒绝接受移植物，并在术后日 (POD) +500 时选择性处死，第 2 组的所有动物在 POD 108 之前都拒绝接受移植物。在第 3 组中，8 只动物中有 3 只发展出长期接受同种异体移植物。在所有组中，肺再灌注后一小时，供体白细胞嵌合在外周血中达到 20% 的峰值。第 1 组在 POD 7 之后保持长时间的嵌合，而第 2 组和第 3 组的嵌合水平此后持续下降。延迟照射有可能提高移植物的长期存活率，但不如围手术期调理方案有效。