Studies on Homologous Bone Marrow Transplantation in Irradiated Rabbits

Abstract

White New Zealand rabbits were exposed to 1100 r as a split dose of 600 r followed 24 hours later by 500 r and transplanted with fresh or frozen, lyophilized, sonicated homologous bone marrow. Fresh marrow was infused 24 hours or 72 hours after x-irradiation. All these animals received antibiotics and, in addition, another group received antibiotics only. Donors were females differing, on the basis of Cohen’s Hg^ADF allelomorphic system for erythrocytes, from the recipient males. It was therefore possible to follow the success of the graft qualitatively by the occurrence of female heterophil leukocytes, and semiquantitatively by the presence of donor erythrocytes in the circulation of the recipient. Complete correlation between these two parameters did not occur: sometimes leukocytes, sometimes erythrocytes, and sometimes both elements of the donor were found in the circulation of the recipient. If animals retained their graft, complete repopulation with donor erythrocytes occurred at about the tenth week postirradiation and transplantation. The number of donor leukocytes present in the blood of the chimeras suggested a mixed population. Not only were the grafts often incomplete but in many instances they were not permanent. Initially, all but one animal had a successful graft, but of the 18 animals which had received fresh marrow and survived at least 12 weeks 12 retained their graft. Much better results in terms of permanent takes were obtained when the marrow was infused 24 hours, rather than 72 hours, after x-irradiation. Nonviable marrow had no protective effect, whereas antibotics did decrease the mortality. An immune hemolytic anemia was shown to be part of the secondary disease syndrome. Antibodies specific to stored recipient erythrocytes were found in the sera of all chimeras between the third and seven weeks after transplantation. When donor erythrocytes were used, the test was positive on only 3 animals. These 3 animals died between the third and eighth weeks postirradiation with secondary disease. When stored recipient erythrocytes were thawed, labeled with Cr⁵¹, and infused into chimeras three or four weeks after irradiation and transplantation, they had in every case a greatly shortened half-life commensurate with a hemolytic anemia. Donor erythrocytes were infused into other chimeras and in all but one instance had a normal half-life. It is suggested that all rabbit chimeras develop secondary disease to some extent, as indicated by a weight loss and fall in hematocrit, but that the situation is not necessarily fatal, except when recovery of the host’s immune mechanism occurs in the presence of a graft which is actively producing antibodies against the host.