GRAFT-VERSUS-HOST REACTIVITY AND GRAFT-VERSUS-LEUKEMIA EFFECT IN MURINE ALLOGENEIC BONE-MARROW CHIMERAS CONDITIONED WITH TOTAL-BODY IRRADIATION OR TOTAL LYMPHOID IRRADIATION

To investigate whether graft-versus-host reactivity (GVHR) and the gra ft-versus-leukemia (GVL) effect can be differentiated, C3H-->AKR mixed bone marrow (BM) chimeras were prepared using two different condition ing regimens, Total body irradiation (TBI) chimeras were induced by in fusing 5x10(6) T cell depleted syngeneic AKR BM cells together with 15 x10(6) non T cell depleted allogeneic C3H BM cells 1 day after a singl e fraction of 10.5 Gy TBI. Total lymphoid irradiation (TLI) chimeras w ere prepared by injecting only 15x10(6) non T cell depleted C3H BM cel ls after 10 daily fractions of 2 Gy TLI. Both groups of chimeras were healthy, without clinical or histological signs of graft-versus-host d isease (GVHD), In both groups, clonal deletion of antihost-reactive do nor type T lymphocytes was found, Whereas TBI chimeras did resist reje ction by host type splenocytes injected 2 months after transplantation , TLI chimeras did not, As the latter phenomenon is believed to reflec t remaining GVHR, TLI chimeras did have a lower remaining GVHD capacit y than TBI chimeras, Nevertheless, TLI chimeras survived significantly longer after host type leukemia challenge (injection of 6x10(6) AKR l ymphoma cells), The better survival of the TLI chimeras was not due to the radiation regimen, because TLI or TBI conditioned syngeneic AKR-- >AKR BM recipients did succumb equally rapidly after AKR lymphoma inje ction. Donor type (C3H) lymphokine-activated killer cell activity, how ever, was higher in TLI chimeras and may explain the better GVL activi ty in TLI mice, This model thus illustrates that GVHD and GVL effects can be dissociated and are differentially influenced by the conditioni ng regimen used for BM transplantation.