Tissue transplantation in pyridoxine-deficient mice
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Abstract
The process by which tissue transplants are rejected by the host is believed to involve an antigen-antibody reaction. This hypothesis is strengthened by successful transplantations carried out in agammaglobulinemic patients. Also, in normal subjects, second set homografts are rejected much earlier than are the initial grafts, indicating that antibodies are already present at the time of second grafting. The time of rejection of the first set of grafts is approximately the same as the time required for the demonstration of circulating antibodies after the parenteral administration of a foreign protein, about ten to fourteen days. It has been shown that the second-set phenomenon can be reproduced by passive sensitization of the future recipient to the future donor.
Although it has been indicated that rejection of transplants is believed to involve an antibody-antigen reaction, no circulating antibodies to skin or other transplanted tissues have been demonstrated. However, the rejection is believed due to tissue, non-circulating antibodies.
Homograft survival depends on other factors as well as presence or absence of antibody. Genetic differences have been shown to be of great importance by many workers. Successful grafts may be made between identical twins or among highly inbred strains of animals. Tolerance can be induced by injecting the fetal or neonatal animal with cellular extracts from the future donor.
It has been demonstrated recently that (1) tolerance is due to a central failure of the imununologic response and (2) the antigens in the homograft do not adapt but continue to produce stimuli in the original form.
In agammaglobulinemic patients lymph nodes are abnormal, usually being small and poorly developed and plasma cells are absent from inflammatory exudates, bone marrow and lymph nodes. A distinct lymphoid atrophy together with absence of plasma cells has been demonstrated experimentally in mice fed a pyridoxine-deficient diet. Recent investigations have emphasized the importance of the plasma cell in antibody production. Pyridoxine-deficiency in mice can be produced in a relatively short time by the use of the anti-metabolite, desoxypyridoxine.
It is possible to produce a high degree of anaphylactic sensitivity to foreign protein in mice by combining Hemophilis pertussis with the antigen in the sensitization procedure.
Methods and Results.
Pyridoxine deficiency has been produced in mice by administration of desoxypyridoxine in conjunction with a pyridoxine-deficient diet.
The production of anaphylactic sensitivity in pyridoxine deficient mice has markedly inhibited: a mortality rate of 100% was obtained in control animals while only 23% of the deficient mice died of anaphylactic shock.
Antibody titrations of the sera of sensitized mice by the Boyden technique resulted in positive reactions in the control sera to a dilution of greater than 1:640, while the sera of the deficient mice was positive to a dilution of only 1:160.
A highly significant statistical difference in survival time of skin homografts was obtained between control and deficient mice. The mean survival time found for grafts in control albinos was 16 days while that for the deficient ones was 22 days.
In adrenalectomized animals the mean survival time for homografts in albino controls was 17 days while that for the deficient ones was 24 days.
In the case of homografts exchanged between strains, no difference was found between albino to black transfers and black to albino transfers in the controls. The mean survival time for the grafts in both instances was 10 days. In the deficient groups the mean survival time for black grafts to white mice was 23 days and the mean for white grafts to black mice was 21 days.
When adrenalectomies were performed along with homograftings between strains, no difference was found in either the control or deficient groups. The mean for all four groups was about 16 days.
No significant difference has found between survival times of homografts made between normal male mice and those made between female controls. The mean for the male mice was 13 days and for the female mice it was 16 days.
Autografts of Swiss-Webster mice appeared to slough at about the nineteenth day but two months after grafting, 65% of the sites were regrowing hair in the direction in which the grafts had been oriented.
A definite depression of anaphylactic sensitivity and a marked decrease in antibody titer to foreign protein has been demonstrated in pyridoxine-deficient mice. A statistically significant difference in lengthening of survival time of homografts has been observed in pyridoxine-deficient mice as compared with their controls.
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Thesis (M.A.)--Boston University
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