Transplantation tolerance in primates following total lymphoid irradiation and allogeneic bone marrow injection. I. Orthoptic liver allographs
Fractionated total lymphoid irradiation (TLI) and allogeneic bone marrow (BM) injection have been reported to produce stable chimerism without graft-versus-host disease (GVHD) in inbred mice and rats and mongrel dogs, and transplantation tolerance for skin and heart grafts in rodents. This concept has been studied in outbred chacma baboons receiving orthotopic liver allografts with the use of five different irradiation protocols. Eight fractions of 200 rad to the whole torso, followed immediately by allogeneic BM injections, and liver grafts from the BM donors 3 to 4 weeks later resulted in markedly prolonged survivals of 63 to 106 days in four baboons (median survival of untreated controls 19 days). Only one of the four animals died directly from the effects of rejection. BM chimerism was demonstrated in two baboons. There were no clinical or histological signs of GVHD in any of the animals. Two fractions of TLI, totaling 800 rad, 23 hr apart and followed immediately by BM injection and liver grafting resulted in profound thrombocytopenia and death form intraperitoneal hemorrhage in four of five baboons. In one animal BM injection and liver transplantation were delayed for 75 days. The baboon is still alive more than 6 months later. Three groups received single doses of 300, 400, and 500 rad to the whole torso, followed by allogeneic BM injections 1 and 2 weeks later, and liver transplants from their BM donors after an additional 3 to 4 weeks. The four baboons receiving 300 rad survived for 42, 86, 123, and >180 days. Two of the four baboons receiving 400 rad died of septic intraabdominal complications with minimal or no evidence of rejection. Fourh of the five baboons receiving 500 rad died from rejection.
- Research Organization:
- Univ. of the Witwatersrand Medical School Johannesburg, South Aqfrica
- OSTI ID:
- 5246528
- Journal Information:
- Transplantation; (United States), Vol. 29:5
- Country of Publication:
- United States
- Language:
- English
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62 RADIOLOGY AND NUCLEAR MEDICINE
59 BASIC BIOLOGICAL SCIENCES
GRAFT-HOST REACTION
BIOLOGICAL RADIATION EFFECTS
IMMUNOSUPPRESSION
RADIOINDUCTION
LYMPHATIC SYSTEM
LYMPHOPENIA
RADIOTHERAPY
SIDE EFFECTS
APES
BONE MARROW
COBALT 60
DOSE-RESPONSE RELATIONSHIPS
FRACTIONATED IRRADIATION
GAMMA RADIATION
INJECTION
LINEAR ACCELERATORS
LIVER
PARTIAL BODY IRRADIATION
RADIATION CHIMERAS
RADIATION DOSES
SURVIVAL TIME
TOLERANCE
TRANSPLANTS
ACCELERATORS
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL EFFECTS
BODY
CHIMERAS
COBALT ISOTOPES
DIGESTIVE SYSTEM
DISEASES
DOSES
ELECTROMAGNETIC RADIATION
EXTERNAL IRRADIATION
GLANDS
HEMATOPOIETIC SYSTEM
HEMIC DISEASES
INTAKE
INTERMEDIATE MASS NUCLEI
INTERNAL CONVERSION RADIOISOTOPES
IONIZING RADIATIONS
IRRADIATION
ISOMERIC TRANSITION ISOTOPES
ISOTOPES
LEUKOPENIA
MAMMALS
MEDICINE
MINUTES LIVING RADIOISOTOPES
MOSAICISM
NUCLEAR MEDICINE
NUCLEI
ODD-ODD NUCLEI
ORGANS
PATHOLOGICAL CHANGES
PRIMATES
RADIATION EFFECTS
RADIATIONS
RADIOISOTOPES
RADIOLOGY
SYMPTOMS
THERAPY
TISSUES
VERTEBRATES
YEARS LIVING RADIOISOTOPES
560152* - Radiation Effects on Animals- Animals
550603 - Medicine- External Radiation in Therapy- (1980-)
551000 - Physiological Systems