A ROLE FOR CD95 LIGAND IN PREVENTING GRAFT-REJECTION

TESTIS is a remarkable immune-privileged site, long known for its abil ity to support allogeneic and xenogeneic tissue transplants(1-4). Here we have investigated the molecular basis for testis immune privilege. Testis grafts derived from mice that can express functional CD95 (Fas or Ape-1) ligand(5-8) survived indefinitely when transplanted under t he kidney capsule of allogeneic animals, whereas testis grafts derived from mutant gld mice, which express non-functional ligands(8,9), were rejected. Further analysis of testis showed that CD95 ligand messenge r RNA is constitutively expressed by testicular Sertoli cells, and tha t Sertoli cells from normal mice, but not gld mice, were accepted when transplanted into allogeneic recipients. CD95 ligand expression in th e testis probably acts by inducing apoptotic cell death of CD95-expres sing, recipient T cells activated in response to graft antigens. These findings indicate that CD95 ligand could be used to create immune-pri vileged tissue for a variety of transplant uses.