TISSUE-SPECIFIC DIFFERENCES IN THE ESTABLISHMENT OF TOLERANCE - TOLEROGENIC EFFECTS OF LUNG ALLOGRAFTS IN RATS

With the increasing frequency of transplantation of two or more organs into a single recipient, it has become evident that different organs are rejected with different kinetics. In this study the kinetics of sk in, lung, and heart allograft rejection were compared in a rodent mode l. To study the influence of different allografts on the recipient's i mmune system, simultaneous or sequential skin, lung, or heart transpla nts were performed in various combinations, using DA rats as recipient s for PVG allografts. Recipients receiving primary allografts were tre ated postoperatively with ten doses of cyclosporine (CsA) or preoperat ively with 4 doses of rabbit antirat thymocyte globulin (ATG). Subsequ ent transplants were performed a minimum of 40 days later without addi tional immunosuppression. All primary skin allografts and 60% of prima ry lung allografts were rejected, while 100% of the heart allografts w ere accepted indefinitely. Recipients of primary skin allografts rejec ted subsequent skin, lung, or heart allografts with accelerated kineti cs. Recipients of primary heart allografts accepted subsequent skin, l ung, and heart allografts indefinitely without further immunosuppressi on. Surprisingly, animals that had rejected a primary lung allograft a ccepted subsequent skin or heart allografts indefinitely. Simultaneous ly transplanted skin and lung allografts were concordantly rejected. H owever, these animals accepted a subsequent heart allograft indefinite ly, suggesting a strong tolerizing effect of lung allografts. Our resu lts indicate that tissue-specific differences are critical, not only i n determining acceptance or rejection of a primary allograft but also in determining the fate of subsequent allografts.