Specificity of cellular migration into cardiac allografts in rats

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, we have examined this problem by two methods: (1) detection of preferentially accumulating cells selectively cytotoxic to allografts bearing specific transplantation antigens as compared with "third-party" allografts; and (2) examination of trafficking patterns of separate radiolabeled populations of sensitized cells adoptively transferred into double heart-grafted recipients. In the first 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 less than 0.05). Because the question of cross-reactivity betweeen 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 third-party labels was measured in each graft. In this second series of experiments, significant (P less than 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.