Induction of unresponsiveness to major transplantable organs in adult mammals
Transplantation of renal allografts obtained from prospectively selected genotypically DLA-identical donors into supralethally irradiated dogs reconstituted with their own stored bone marrow has produced a state of unresponsiveness to these kidneys in the recipients. Eleven of 18 kidneys transplanted at 12 hours after marrow replacement currently survive with normal function and maintain life in the recipients. Similar results occurred in eight of 13 allografts transplanted at 28 hours and in eight of 13 kidneys grafted at 36 hours after marrow replacement. Only four of 16 recipients of kidneys transplanted at the time of marrow replacement were unresponsive to their allografts. Similarly, only five of 19 recipients of kidneys placed in irradiated dogs at 40 hours before marrow replacement accepted such allografts. When kidney transplants were placed into the recipients 20 hours before removal of marrow, irradiation, and reconstitution with stored marrow, only three of 21 dogs became unresponsive to such allografts. In five of 12 instances, the recipients were also unresponsive to skin allografts obtained from their respective kidney donors. Rejection of these skin grafts had no detectable effect on the function and survival of kidney allografts from the same source. Seven of eight skin grafts obtained from other DLA-identical donors were rejected. Eleven DLA-incompatible skin allografts placed on the recipients at the same time were rejected within 11 to 20 days. Supralethal total body irradiation and bone marrow replacement can establish in the adult canine host a privileged phase of immunological reactivity during which exposure to alloantigens produces specific long-term unresponsiveness rather than sensitization. The use of stored autologous rather than allogeneic bone marrow for reconstitution of the irradiated recipient eliminates the hazards of GVH complication usually associated with this procedure.
- Research Organization:
- State Univ. of New York, Stony Brook
- OSTI ID:
- 5288624
- Journal Information:
- Ann. Surg.; (United States), Journal Name: Ann. Surg.; (United States) Vol. 190:4; ISSN ANSUA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
560152* -- Radiation Effects on Animals-- Animals
62 RADIOLOGY AND NUCLEAR MEDICINE
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
BIOLOGICAL EFFECTS
BIOLOGICAL RADIATION EFFECTS
BODY
BONE MARROW
DOGS
ELECTROMAGNETIC RADIATION
EXTERNAL IRRADIATION
GENOTYPE
GRAFT-HOST REACTION
GRAFTS
HEMATOPOIETIC SYSTEM
IMMUNE REACTIONS
IMMUNITY
IMMUNOSUPPRESSION
IONIZING RADIATIONS
IRRADIATION
KIDNEYS
MAMMALS
ORGANS
RADIATION EFFECTS
RADIATIONS
RADIOINDUCTION
SKIN
TIME DEPENDENCE
TISSUES
TRANSPLANTS
VERTEBRATES
WHOLE-BODY IRRADIATION
X RADIATION