PROTECTIVE GENES EXPRESSED IN ENDOTHELIAL-CELLS OF 2ND HAMSTER HEART-TRANSPLANTS TO RATS CARRYING AN ACCOMMODATED FIRST GRAFT

Accommodation refers to survival of a xenograft despite the presence o f anti-donor organ antibodies and complement. We have recently shown t hat accommodation of a hamster heart transplanted to a rat receiving s hort-term cobra venom factor (CVF) and continuing cyclosporine A (CyA) therapy is associated with i) the expression in the endothelial cells (EC) and smooth muscle cells of the graft of a number of ''protective '' genes, ii) a prominent intragraft Th2 cytokine profile, and ill) th e relatively heavy deposition of IgG2c antibodies on the EC of the gra ft. In contrast, rejecting grafts do not express the protective genes, have a Th1 cytokine profile, and apparently have lesser amounts of Ig G2c. These ,findings are consistent with host factors (Th2 cytokines a nd IgG2c) contributing to xenograft accommodation. To test whether the se host factors may predispose to the development of accommodation, we placed a second hamster heart into each of 12 rats carrying a survivi ng first heart; recipients were, at the time, receiving only CyA. Wher eas first grafts transplanted to rats receiving only CyA survive for 3 to 4 days, 11 out of 12 second transplants survived more than 20 days , and the other survived for 7 days. Nine of the twelve were not rejec ted: of these, four were removed between day 35 and 132 for study, and the remainder are still beating at 35 to 52 days. The surviving secon d hearts we studied had accommodated in that the picture on immunopath ology was the same as for surviving first hearts. We suggest that the Th2 cytokines and perhaps the IgG2c response are factors in allowing p rolonged survival of the second grafts and, further, that these factor s contribute to the expression in the EC and smooth muscle cells of th e surviving second hearts of the protective genes.