The role of Fas ligand as an effector molecule in corneal graft rejection

Abstract

Previous studies have shown that the expression of Fas ligand (FasL; CD95L) by donor corneas is critical to their survival when placed on allogeneic recipients. Since there have been reports that the cornea expresses Fas, we tested the idea that FasL on lymphoid cells could be an effector molecule during rejection episodes. When FasL defective BALB/c-gld mice were engrafted with allogeneic corneas, significantly more of these corneas were accepted than by normal BALB/c mice. However, this was not due to impaired FasL-mediated effector function in these mice as the allogeneic corneas did not express detectable Fas by Western blot or RT-PCR analysis. Furthermore, donor corneas without Fas were given no survival advantage, but were rejected similar to wild-type donor allogeneic corneas. Examination of the T cell compartment in gld mice revealed that these cells express higher levels of Fas and are more susceptible to Fas-mediated death than wild-type cells. These results indicate that FasL is not an effector molecule in corneal graft rejection and that gld mice show reduced graft rejection due to greater susceptibility of their T cells to Fas-mediated apoptosis.

Immunological Disruption of Antiangiogenic Signals by Recruited Allospecific T Cells Leads to Corneal Allograft Rejection

“…FasL-mediated apoptosis and perforin may also contribute to CD4 + T cell-mediated corneal allograft rejection. However, even in the absence of either of these effector molecules, mice still readily reject corneal allografts (13)(14)(15)(16)(17). This suggests that multiple effector mechanisms are involved in corneal allograft rejection.…”

IL-1β regulates the mouse Fas ligand expression in corneal endothelial cells

“…In addition, it was noted that inflammatory cells infiltrating into submucosal and peribronchial regions of the upper and lower airways in the FasL deficient mice (gld mice). In eyes, several studies have been shown that the FasL can be expressed constitutively in corneal epithelial and endothelial cells [22,24,28] , and may play a critical role in controlling inflammatory cells infiltration in eye tissue. Consistent with this, Stuart et al [22] demonstrated that wild type but not gld corneal grafts survive after allogeneic transplantation.…”

“…Consistent with this, Stuart et al [22] demonstrated that wild type but not gld corneal grafts survive after allogeneic transplantation. Protection from immune-mediated tissue rejection is believed to result from the ability of constitutively expressed graft FasL to induce the apoptosis of infiltrating Fas + host effects T cells [22][23][24] . A number of studies have shown that IL-1 is a potent pro-inflammatory cytokine and is actively involved in inflammation process including immune cell recruitment and induction of other inflammatory cytokines such as IL-8, TNF-α, IL-6 and prostaglandin E2 [31] .…”

“…These results suggested that gld mice do not demonstrate immune privilege status in the eye and testis [2] . Studies have also shown that during cornea transplantation, FasL of corneal cells in grafts induced apoptosis of infiltrating hose immune cells, thereby improving corneal allograft survival [22][23][24] . These findings suggested that regulation of FasL expression might play an important role in controlling the outcome of corneal allografting.…”

Prolongation of corneal allograft survival by CTLA4-FasL in a murine model

“…However, CTLA4-FasL proteins displayed a potential function of tolerance induction for the utility of FasL in transplantation and conferring immune privilege [7,29]. Healthy mouse corneal allografts surviving beyond 8 weeks, reported by Yamada et al [14], was evidence of donor-specific tolerance.…”