人→猪脾块移植嵌合细胞的体内转归

The Status of Chimeric Cells in Human to Pig Spleen Transplantation Model

目的 建立人→猪异种移植物抗宿主反应 (GVHD)模型来模拟猪→人异种移植时人免疫系统对猪的攻击。方法 以中国内江猪为实验动物 ,经环磷酰胺静注行免疫抑制后 ,腹膜腔内植入人脾块悬液 ,术前、术后定期采集猪外周血行血常规检查监测猪被免疫抑制程度。行流式细胞术检查监测人细胞在猪外周血中嵌合情况 ,行细胞介导的淋巴细胞毒试验动态监测人抗猪和猪抗人的细胞毒活性。结果 各试验猪存活良好 ,给药后 4 d各猪外周血白细胞总数可降至正常值的 15 %左右 ,移植后第 2天和第 2周左右 ,人细胞在猪体内可形成两个较明显的嵌合高峰 ,尽管人抗猪淋巴细胞毒性于术后 2周时有明显升高 ,但在术后 1个月内猪抗人淋巴细胞毒性始终明显高于人抗猪淋巴细胞毒性。结论 人→猪脾块移植后 ,受猪体内的供受细胞呈现一个两元 (猪细胞、人细胞 )三态 (微嵌合、宿主抗移植物反应、移植物抗宿主反应 )

Objective To establish a human to pig xenotransplantation GVHD model to simulate the human anti pig grafts immunoreaction in vivo. Methods The Chinese Neijiang pigs were immunosuppressed by CTX followed by the transplant of human spleen slices into pig's peritoneal cavity. We tested the routine items of the pigs' peripheral blood regularly, monitored the chimeric level by FCM, and examined the cytotoxicities of both human anti pig and pig anti human by CML. Result The pigs all survived during the experimental period. The PBWBC decreased by 85% after 4 days of giving CTX. The chimeric peaks appeared on day 2 and day 14 after transplant. The cytotoxicity of human anti pig was always less than that of pig anti human, although it increased significantly after 2 weeks of transplant. Conclusion There might be a dynamic changeable balance of HVG, microchimerism, and GVH due to the reaction between the chimeric human cells and the pig cells in the human to pig spleen xenotransplantation model.