SUBLETHAL FRACTIONATED TOTAL-BODY IRRADIATION AND DONOR BONE MARROW INFUSION FOR INDUCTION OF ALLOGRAFT TOLERANCE

Abstract

Tolerance to skin allografts across he strong histocompatibility barrier H-2b to H-2d was achieved with sublethal fractionated total-body irradiation, FTBI, delivered to H-2d mice in 3 doses of 250 rads within 24 hr, followed by transfusion of 3x102 H-2 donor bone marrow (BM) cells. H-2b skin allografts were applied within 48 hr after the initial radiation. 70% of the mice became long-term (< 180-day) survivors with fur-bearing grafts. Marked interexperiment variability in survival rates suggested that infection was the major cause of death in this model and lower weight gain and survival rates for allogenic BM vs. media-treated controls suggested that graft-versus-host disease (GVHD) was also a factor. The observation, however, that long-term survivors (70% of all mice) gained weight and appeared healthy suggested that the GVHD might be self-limiting. Chimeric analysis revealed that approximately 25% of spleen cells were of donor origin, both at short-term (6 weeks) and long-term (< 1 year) intervals after tolerance induction. In spite of hematopoeitic chimerism, a low incidence of spontaneous tumors, <1%, occurred in the long-term survivors.