Tolerance or rejection: A delicate balance as judged by exposure of heart-transplanted rats to the immunomodulator Linomide (R)

When applied in rodent transplant models most immunosuppressive drugs yield adequate graft protection for as long as the drug is given, and permanent graft survival is often induced. The immunomodulator, Linomide(R), previous ly shown to stimulate T cells and prevent apoptosis, usually reduces or abo lishes both tolerance induction and the graft-protective effect of the immu nosuppressive drug. By chance, we observed that Linomide(R) alone exerted a modest but unequivocal graft-protective effect in the BN to WF strain comb ination. This finding was analysed by simple genetic mapping of rat strains . Untreated WF recipients kept BN grafts for a median of 8 days, whereas Li nomide(R) treatment prolonged graft survival to 12.5 days (P = 0.0001). In control groups (DA to LEW, BN to LEW, DA to WF and WF to BN), median graft survival was 5.5-7 days irrespective of whether Linomide(R) was given. Howe ver, the BN to F1 (LEW x WF) combination also manifested slightly longer gr aft survival in the presence of Linomide(R). F1 (BN x WF) to WF grafts surv ived a median of 15 days without Linomide(R) and 36 days with Linomide(R) t reatment. Both in the presence and absence of Linomide(R) two of the contro l graft combinations [F1 (BN x DA) to WF and F1 (BN x WF) to BN] manifested 6-7-day graft survival. Taken together, our results suggest a delicate bal ance between unresponsiveness and rejection, while a single agent (Linomide (R)) may either cause on its own longterm survival of allografts in one set ting or rejection despite optimal immunosuppression in another setting.