Immunologic studies of canine bone marrow chimeras.
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Biomedical subjects
Publications and source records attributed to F T Rapaport.
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20 Cooperstown beagles of known DL-A genotypes (B" dogs) were exposed to supralethal total body irradiation and received a bone marrow allograft from a DL-A identical donor (A" dog); the resulting chimeras have survived uneventfully for 882, 1466 days, with no evidence of secondary disease, and have been tolerant to kidney and skin allografts obtained from the donor of marrow. Treatment of "A" dogs with serum obtained from their long-term "B" chimeras had no significant effect upon the ability of the recipients to reject "B" skin allografts...
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Nine Cooperstown beagles of known DL-A genotypes were exposed to supralethal total-body irradiation and received bone-marrow allografts from DL-A-identical donors. Four to 5 months later, the resulting chimeras received orthotopic cardiac allografts from their corresponding donors of marrow. Six chimeras died of operative complications in the immediate postoperative period. The other 3 chimeras survived from 173 to 547 days; 1 dog died at 173 days as a result of right-sided heart failure, secondary to stenosis at the site of the pulmonary artery anastomosis. The other two recipients continue to be active and healthy at 545 and 547 days. The results indicate that dogs can be rendered specifically tolerant to orthotopic cardiac allografts by supralethal total-body irradiation and the transplantation of marrow obtained from the prospective allograft donor.
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Heterotopic hepatic transplantation was performed in 26 pairs of littermate and non-littermate mongrel dogs selected by serological criteria of DL-A compatibility. No immunosuppression was given. In non-littermates, 11 recipients of DL-A incompatible allografts survived 10-22 days (mean 13.4 days). Mean serum bilirubin rose by the 6th day. Three recipients of DL-A compatible allografts survived 13, 41, and 60 days, (mean 38 days). Mean serum bilirubin rose by the 8th day. In littermates, 5 recipients of DL-A incompatible allografts survived 7-12 days (mean 10.2 days) and mean serum bilirubin rose by the 6th day. Four recipients of DL-A compatible allografts from phenotypically DL-A non-identical donors survived 58, 82, 90 and 128 days (mean 89.5 days). Mean serum bilirubin rose by the 29th day. In contrast, 3 recipients of DL-A phenotypically identical allografts survived 171, 536 and over 636 days respectively, with normal mean serum bilirubin levels. The results confirm the role of the DL-A system in hepatic transplantation in mongrel dogs, and suggest that this dog population may constitute a suitable experimental model parallelling the current situation with regard to HL-A compatibility testing in outbred human subjects. The relatively long survival of DL-A compatible heterotopic hepatic allografts, compared with similar transplants of skin, kidney and heart, also suggests a need for studies of possible alteration in parameters of humoral and cellular reactivity in these recipients.
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