FAS LIGAND, TUMOR-NECROSIS-FACTOR-ALPHA EXPRESSION, AND APOPTOSIS DURING ALLOGRAFT-REJECTION AND TOLERANCE

Background. Cytotoxic T cells can induce target cell lysis and apoptos is by different pathways. The interactions of CD95 antigen (Fas) with its ligand (CD95L) and of tumor necrosis factor (TNF)-alpha with its r eceptor (TNF-R1) lead to apoptotic cell death. Recently, conflicting s tudies have been published concerning the expression and the role of C D95L in allograft rejection and tolerance. Methods. In this study, the intragraft expression of CD95/CD95L and TNF-alpha and the frequency a nd distribution of apoptotic cells were compared in a model of heterot opic cardiac allograft in the rat in which recipients were either not treated (acute rejection) or pretreated with donor-specific blood tran sfusion (tolerant). Results. in the acutely rejected allografts, a pea k in the expression of CD95L and TNF-alpha and in the number of apopto tic cells was observed during the first week after transplantation; ap optotic cells were confined to graft-infiltrating cells. In the tolera ted allografts, how ever, levels of graft-infiltrating cell apoptosis and CD95L and TNF-alpha expression during the same period of time were dramatically lower. The expression of Fas was constitutive and was no t modulated during acute rejection or tolerance. Conclusion. This down -regulation of CD95L and TNF-alpha in allografts rendered tolerant by donor-specific transfusion suggests a role for apoptosis-inducing path ways in acute allograft rejection.