Genetics of the blood transfusion effect on heart allografts in rats

Abstract

Working with the recently available recombinant haplotypes of the rat major histocompatibility complex (MHC)--RT1, we investigated the effect of various types of blood transfusion (BT) on allograft prolongation, including blood identical for the whole RT1 haplotype with that of the donor or for only a part of it. One or two milliliters of donor blood significantly prolonged graft survival in the (LEW X BN)F1----LEW or the LEW X 1W----LEW X 1A combination. The optimal regimen consisted of two BTs given 15 and 7 days prior to grafting; BTs given at day -30 were ineffective. A BT given on the day of the operation was effective, but sequential BTs after grafting did not further increase graft survival. In the (LEW X BN)F1----LEW combination, blood from congenic LEW X 1N rats significantly prolonged graft survival, but third-party BTs were ineffective or had only a borderline effect when transfused (1 ml, 8 times) within the three months before transplantation. This showed the major role of the RT1 system as well as the specificity of the model. Although the survival of LEW X 1A heart grafts transplanted into LEW X 1W recipients could not be significantly prolonged by donor blood, with the reverse--and "weaker"--combination (LEW X 1W----LEW X 1A), 2 ml of donor blood led, in all cases, to greater than 100 days graft survival. In this last combination, third-party BT (LEW X 1N) was again totally ineffective. Blood from RT1-recombinant rats was used to test the role of the respective RT1.A, B, and C regions, in the enhancing effect. BTs from LEW X 1AR2 or LEW X 1WR2 recombinants--sharing, respectively, RT1.C and RT1.A with the graft donor--were only moderately effective, as compared with BTs from the graft donor. On the other hand, LEW X 1WR1 BTs--sharing the RT1.A and RT1.B regions with the graft donor--had a much more powerful effect on heart survival. The results strongly suggest that the RT1.B region (coding for Ia-like antigens) must be shared by the graft and blood donor in order to mediate a significant graft prolongation.