Allograft rejection is one of the major obstacles in transplantation. During rejection, the immune cells destroy the foreign cells. Recently, methods are being developed to prevent transplant rejection. The initial clue as how to prevent transplant rejection has come from the observation that expression of CD-95 (Fas or Apo-1) ligand (FasL) in the transplant, by virtue of induction of apoptosis of immune cells carrying the Fas, acts as a protective mechanism against rejection. Bellgrau et al, reported that presence of CD-95 ligand on the Sertoli cells protected the testis from being rejected by the allogeneic host. Testis grafts from mice that expressed functional CD95 ligand survived indefinitely when transplanted under the kidney capsule of allogeneic animals, whereas testis grafts derived from mutant gld mice, which express non-functional ligand, were rejected. These findings indicated that CD95 ligand could be used to induce an immune-privileged status in the tissues. Griffith et al also reached the same conclusion when testing another immune-priviledged site, the eye. Mononuclear cells which, in response to viral infection, entered the anterior chamber of the eye underwent apoptosis. This process was dependent on Fas (CD95)-Fas ligand (FasL) and did not result in tissue damage. On the other hand, in gld mice, which lack functional FasL, viral infection led to inflammation and invasion of ocular tissues. However, in these animals, no evidence of apoptosis was detected. For gaining additional proof that Fas-Fas ligand interaction is involved in the rejection, the authors conducted further experimentation. Tumor cells that were Fas-positive and not Fas-negative tumor cells were killed by apoptosis when placed in the anterior chamber of the eyes of normal but not FasL-negative mice. The FasL is expressed on the trophoblasts in the free floating villi, anchoring villi and cytotrophoblastic islands. Based on these findings, Runic et al suggest that local expression of FasL on cytotrophoblasts may be a mechanism for immune tolerance and the fetal survival. The hypothesis that Fas-FasL interaction is invovled in transplant rejection was put to test by Lau et al. These authors engineered myoblasts to express FasL in mice. Co-transplantation of the syngeneic myoblasts that expressed FasL along with allogeneic islets of Langerhans protected the islets from rejection and maintained normoglycemia for more than 80 days in mice with diabetes. The islets were rejected when transplantated with myoblasts not expressing FasL. These finidings show that FasL provide immune-protection against rejection and offer the opportunity to overcome the transplant rejection.
REFERENCES:
Bellgrau, 1995. A role for CD95 ligand in preventing graft rejection. Nature 377, 630-632 (1995) [96026301]
Griffith, 1995. Fas ligand-induced apoptosis as a mechanism of immune privilege. Science 270, 1189-1192 (1995) [96072969]
Runic R, Lockwood CJ, Ma Y, Dipasquale B, Guller S: Expression of Fas ligand by human cytotrophoblasts: implications in placentation and fetal survival. J Clin Endocrinol Metab 81, 3119, 1996
Lau HT, Yu M, Fontana A, Stoeckert CJ Jr: Prevention of islet allograft rejection with engineered myoblasts expressing FasL in mice. Science 273, 109-112, 1996
Allograft rejection is one of the major obstacles in transplantation. During rejection, the immune cells destroy the foreign cells. Recently, methods are being developed to prevent transplant rejection. The initial clue as how to prevent transplant rejection has come from the observation that expression of CD-95 (Fas or Apo-1) ligand (FasL) in the transplant, by virtue of induction of apoptosis of immune cells carrying the Fas, acts as a protective mechanism against rejection. Bellgrau et al, reported that presence of CD-95 ligand on the Sertoli cells protected the testis from being rejected by the allogeneic host. Testis grafts from mice that expressed functional CD95 ligand survived indefinitely when transplanted under the kidney capsule of allogeneic animals, whereas testis grafts derived from mutant gld mice, which express non-functional ligand, were rejected. These findings indicated that CD95 ligand could be used to induce an immune-privileged status in the tissues. Griffith et al also reached the same conclusion when testing another immune-priviledged site, the eye. Mononuclear cells which, in response to viral infection, entered the anterior chamber of the eye underwent apoptosis. This process was dependent on Fas (CD95)-Fas ligand (FasL) and did not result in tissue damage. On the other hand, in gld mice, which lack functional FasL, viral infection led to inflammation and invasion of ocular tissues. However, in these animals, no evidence of apoptosis was detected. For gaining additional proof that Fas-Fas ligand interaction is involved in the rejection, the authors conducted further experimentation. Tumor cells that were Fas-positive and not Fas-negative tumor cells were killed by apoptosis when placed in the anterior chamber of the eyes of normal but not FasL-negative mice. The FasL is expressed on the trophoblasts in the free floating villi, anchoring villi and cytotrophoblastic islands. Based on these findings, Runic et al suggest that local expression of FasL on cytotrophoblasts may be a mechanism for immune tolerance and the fetal survival. The hypothesis that Fas-FasL interaction is invovled in transplant rejection was put to test by Lau et al. These authors engineered myoblasts to express FasL in mice. Co-transplantation of the syngeneic myoblasts that expressed FasL along with allogeneic islets of Langerhans protected the islets from rejection and maintained normoglycemia for more than 80 days in mice with diabetes. The islets were rejected when transplantated with myoblasts not expressing FasL. These finidings show that FasL provide immune-protection against rejection and offer the opportunity to overcome the transplant rejection. 
