van Os R, Konings A W, Down J D
Department of Radiobiology, University of Groningen, The Netherlands.
Int J Radiat Biol. 1992 Apr;61(4):501-10. doi: 10.1080/09553009214551261.
Engraftment of donor bone marrow in relation to total body irradiation (TBI) dose was studied in syngeneic (B6----B6), MHC-compatible (BALB.B----B6) and MHC-incompatible allogeneic (BALB/c----B6) murine bone marrow transplantation (BMT) models. For each BMT combination radiation dose-response curves were obtained from stable long-term bone-marrow chimerism using Gpi-1 phenotyping and this was compared with the growth of exogenous CFU-S. Syngeneic engraftment required the lowest TBI doses limited to ablation of host haemopoietic stem cells. Resistance against H-2-compatible allogeneic engraftment was evident at low radiation doses (less than 5.5 Gy) but at 6 Gy and above the level of chimerism was comparable to syngeneic transplants, which indicated effective immunosuppression. Higher TBI doses were needed for engraftment as the immunological barrier was increased using fully H-2-incompatible allogeneic transplants. The high TBI dose (9.5 Gy) needed for suppression of spleen endocolonies in the CFU-S assay meant that rejection of exogenous bone marrow was evident only across the larger immunological barriers. When the fully allogeneic combination was reversed (B6----BALB/c) both CFU-S and chimerism data showed less rejection. The steep dose-response relationships show how engraftment is critically dependent on TBI dose, as well as the genetic disparity between donor and host.
在同基因（B6→B6）、MHC兼容（BALB.B→B6）和MHC不兼容的异基因（BALB/c→B6）小鼠骨髓移植（BMT）模型中，研究了供体骨髓植入与全身照射（TBI）剂量的关系。对于每种BMT组合，使用Gpi-1表型分析从稳定的长期骨髓嵌合体中获得辐射剂量反应曲线，并将其与外源性CFU-S的生长情况进行比较。同基因植入所需的TBI剂量最低，仅限于宿主造血干细胞的消融。在低辐射剂量（小于5.5 Gy）时，对H-2兼容的异基因植入存在抗性，但在6 Gy及以上，嵌合水平与同基因移植相当，这表明免疫抑制有效。随着使用完全H-2不兼容的异基因移植增加免疫屏障，植入需要更高的TBI剂量。CFU-S试验中抑制脾内集落所需的高TBI剂量（9.5 Gy）意味着只有在跨越更大的免疫屏障时，外源性骨髓的排斥才明显。当完全异基因组合颠倒（B6→BALB/c）时，CFU-S和嵌合数据均显示排斥反应较少。陡峭的剂量反应关系表明植入如何严重依赖于TBI剂量以及供体和宿主之间的遗传差异。
