SPECIFICITY OF CELLULAR MIGRATION INTO CARDIAC ALLOGRAFTS IN RATS

Abstract

The question has not been previously investigated as to whether host lymphocytes infiltrate vascularized organ allografts in indiscriminate fashion, or whether they are retained selectively because of specific antigenic recognition sites on their surfaces. By using a dual cardiac allograft model in LEW rats, this problem was examined by 2 methods: detection of preferentially accumulating cells selectively cytotoxic to allografts bearing specific transplantation antigens as compared with 3rd-party allografts; and examination of trafficking patterns of separate radiolabeled populations of sensitized cells adoptively transferred into double heart-grafted recipients. In the 1st series of experiments, using BN and BUF rats as donors, differences in specific cytotoxicity mounted by infiltrating lymphocytes harvested from the appropriate and inappropriate graft were moderately significant (P < 0.05). Because the question of cross-reactivity between BUF and BN antigen was raised, lymphocytes sensitized to BN and WF donors were differentially labeled in vitro with 3H- or 14C-thymidine. After mixture and adoptive transfer, the ratio of specific to 3rd-party labels was measured in each graft. In this 2nd series of experiments, significant (P < 0.001) preferential accumulation of specifically sensitized cells were found in the appropriate vascularized organ allograft. These experiments confirm the results of other experimental models, and demonstrate that sensitized lymphocytes accumulate selectively in specific vascularized organ allografts.