STUDIES OF THE IMMUNOLOGICAL FACTORS INVOLVED IN HOMOLOGOUS TISSUE TRANSPLANTATION. Progress Report, March 1, 1960 to February 28, 1961
Irradiation of canine renal homografts with an average dose of 770 r delivered locally, failed to prolong the functional survival as compared with controls. Split thickness skin homografts placed on dogs rejecting a renal homograft placed in the portal circulation, rejected as second-set grafts indicating that the liver did not effectively modify tissue antigens supplied to it. Canine renal homografts placed in dogs following rejection of split thickness skin homogrsfts ceased functioning in an aversge of 4.5 days, some 50% more rapidly than control grafts not preceded by skin homogrsfts. In these experiments the evidence seems clear that both shin and kidney tissues have the ability to sensitize recipient animals and allow second set rejection to take place. In a large series of animals, it was not shown that 12 mg/hg of 6- mercaptopurine given intravenoualy daily prolonged skin homografts in rabbits, or indeed in any other animal used in the laboratory. In continuation of the screening program, several additional drugs were studied, none of which appear to favorably prolong the life of skin homografts. One human renal homograft was transplanted which functioned in progressive fashion for the life of the patient. Bone was treated to determine the effect of treatment on antigenicity. S/sup 3// sup 5/-ethyl1-cysteine can be incorporated unchanged in the rabbit antibody molecule and into the proteins of an E. Coli mutant. It is apparently metubolized by the wild-type E. Col:and the label is found in the cysteine fraction. The substance arising in lymph nodes as a result of a skin homograft and which, when intradernally injected, causes a cutaneous reaction, was obtained in its active form in a cell-free preparation. Experiments are in progress to localize intracellular antibody on sub-cellular structures using labelled antigens. Antibody of a circulating type is being compared with that of a non- circulating type in this context. The influence of 6-mercaptopurine on immunity was studied in guinea pigs. Three types of immune reactions were examined, viz., the homograft reaction and the delayed and immediate types of immunity evoked by footpad injection of specific precipitates in adjuvant. The following were observed: 6-MP had no influence on skin grafts; under conditions of high levels of immunity it could partially inhibit an Arthus-type skin reaction; only in toxic animals could the delayed skin reaction be innibited; and the immediate skin reactions failed to reflect the circulating antibody level which, in turn, was not affected by the drug. The data are discussed and tentative conclusions are drawn. The ability of the treated guinea pig to form antibody is believed to be essentially unimpaired, but manifestations of immunity requiring the intervention of reticulo-endothelial cells reflect the action of the dmg. (auth)
- Research Organization:
- Western Reserve Univ., Cleveland. School of Medicine
- DOE Contract Number:
- DA-49-007-MD-961
- NSA Number:
- NSA-15-021993
- OSTI ID:
- 4049502
- Report Number(s):
- AD-251706
- Resource Relation:
- Other Information: Orig. Receipt Date: 31-DEC-61
- Country of Publication:
- United States
- Language:
- English
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