RADIATION-DOSE AS A FACTOR IN HOST PREPARATION FOR BONE-MARROW TRANSPLANTATION ACROSS DIFFERENT GENETIC BARRIERS

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 stein cells. Resistance against H-2-compatible allogeneic engraftment was evident at low radiation doses (<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 allogenic 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.