Sublethal fractionated total-body irradiation and donor bone marrow infusion for induction of allograft tolerance
Tolerance to skin allografts across the 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 3 x 10(7) H-2b 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 (greater than 180-day) survivors with fur-bearing grafts. Marked interexperiment variability in survival rates suggested that infection was the major use 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 (greater than 1 year) intervals after tolerance induction. In spite of hematopoietic chimerism, a low incidence of spontaneous tumors, less than 1%, occurred in the long-term survivors.
- Research Organization:
- Veterans Administration Medical Center, Kansas City, MO
- OSTI ID:
- 5776703
- Journal Information:
- Transplantation; (United States), Vol. 39:3
- Country of Publication:
- United States
- Language:
- English
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MICE
GRAFT-HOST REACTION
RADIATION DOSES
SKIN
GRAFTS
BONE MARROW
DOSE-RESPONSE RELATIONSHIPS
IMMUNE REACTIONS
RADIATION CHIMERAS
SPLEEN CELLS
SUBLETHAL IRRADIATION
SURVIVAL TIME
WHOLE-BODY IRRADIATION
ANIMAL CELLS
ANIMAL TISSUES
ANIMALS
BODY
CHIMERAS
DOSES
EXTERNAL IRRADIATION
HEMATOPOIETIC SYSTEM
IRRADIATION
MAMMALS
MOSAICISM
ORGANS
RODENTS
SOMATIC CELLS
TISSUES
TRANSPLANTS
VERTEBRATES
560152* - Radiation Effects on Animals- Animals