Fas-fas-ligand antigen expression and its relationship to increased apoptosis in acute renal transplant rejection.

Abstract

To examine the role of fas-fas-ligand interaction and apoptosis in acute transplant rejection. Pre- and posttransplant renal allograft biopsies were stained by in situ 3-end labeling of DNA for detection of apoptotic cells (TUNEL) and immunohistochemistry techniques were used for demonstration of fas and fas-ligand antigen expression. Posttransplantation apoptosis was significantly increased in acute rejection and acute tubular necrosis (P<0.0001) compared to preimplantation biopsies and biopsies taken from grafts showing dysfunction not attributed to rejection. Fas and fas-ligand expression was demonstrated predominantly in the tubular epithelium. In preimplant biopsies fas was expressed in 11% (4/37) of cases; posttransplantation expression increased to: 44% (8/18) acute rejection, 63% (5/8) acute tubular necrosis, and 38% (5/13) dysfunction without evidence of rejection. Fas-ligand was expressed by 30% (11/37) of preimplant biopsies, posttransplantation expression was reduced in all groups: 17% (3/18) acute rejection, 13% (1/8) acute tubular necrosis, delayed xenograft rejection and 15% (2/13) dysfunction without evidence of rejection. A correlation with fas-1 expression preimplantation and a subsequent absence of acute rejection post transplant was noted (P<0.001). Apoptosis is a feature of acute rejection and acute tubular necrosis. Fas expression is uncommon preimplantation and increases non-specifically post transplant. Fas-1 was expressed by a third of preimplantation biopsies and expression was lost non-specifically post transplant. The expression of fas-ligand preimplantation correlated with an absence of acute rejection episodes posttransplant, suggesting some degree of immune privilege. These data suggest that the fas-fas-1 mediated pathway does not play a specific role in apoptosis during acute rejection. We were unable to find any evidence that the fas-fas-1-mediated pathway has a role in the increased apoptosis seen during acute rejection.