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

Background, To examine the role of fas-fas-ligand interaction and apoptosis in acute transplant rejection, Methods, Pre- and posttransplant renal allograft biopsies were stained by i n situ 3-end labeling of DNA for detection of apoptotic cells (TUNEL) and i mmunohistochemistry techniques were used for demonstration of fas and fas-l igand antigen expression. Results. Posttransplantation apoptosis was significantly increased in acute rejection and acute tubular necrosis (P<0.0001) compared to preimplantatio n biopsies and biopsies taken from grafts showing dysfunction not attribute d to rejection. Fas and fas-ligand expression was demonstrated predominantl y 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) dysfuncti on without evidence of rejection. Fas-ligand was expressed by 30% (11/37) o f preimplant biopsies, posttransplantation expression was reduced in all gr oups: 17% (3/18) acute rejection, 13% (1/8) acute tubular necrosis, delayed xenograft rejection and 15% (2/13) dysfunction without evidence of rejecti on. A correlation with fas-l expression preimplantation and a subsequent ab sence of acute rejection post transplant was noted (P<0.001). Conclusions. Apoptosis is a feature of acute rejection and acute tubular ne crosis. Fas expression is uncommon preimplantation and increases non-specif ically post transplant. Fas-l was expressed by a third of preimplantation b iopsies and expression was lost nonspecifically post transplant. The expres sion of fas-ligand preimplantation correlated with an absence of acute reje ction episodes posttransplant, suggesting some degree of immune privilege. These data suggest that the fas-fas-l mediated pathway does not play a spec ific role in apoptosis during acute rejection. We were unable to find any e vidence that the fas-fas-1-mediated pathway has a role in the increased apo ptosis seen during acute rejection.