Mice Deficient in Functional FasL Expression Demonstrate Increased Survival of Allogeneic Corneal Transplants

Abstract

Abstract: : Purpose: We previously demonstrated that FasL expressed in the cornea plays a role in corneal allograft acceptance inducing Fas⁺ inflammatory cells to undergo apoptosis. In this report, we investigated the effect of functional FasL on the survival of corneal transplants. Methods: Corneal allograft responses were performed with normal BALB/c (H-2^d) and FasL deficient BALB/c-gld mice as recipients of C57BL/6(B6, H-2^b) corneas. Bone marrow chimeras between these recipient mouse strains were used to determine whether corneal allograft responses segregated with bone marrow or non-bone marrow derived cells. We also performed in vitro assays to determine Fas expression and sensitivity to Fas-mediated death for anti-CD3 activated BALB/c and BALB/c-gld splenocytes. Results: BALB/c-gld recipients demonstrated significantly greater survival of B6 allografts than did control mice at 8 weeks post grafting. As anticipated, this difference associated with the phenotype of the bone marrow cells in chimera studies. In contrast, no differences in rejection frequency or kinetics were seen when BALB/c and BALB/c-gld mice were grafted with B6 tail skin. In vitro analysis of activated splenocytes revealed that gld spleen cells were more susceptible to anti-Fas killing one and two days following anti-CD3 activation. Conclusions:These data indicate that BALB/c-gld mice show significantly increased corneal allograft acceptance, but similar responses to skin allografts than do normal BALB/c mice. We propose that this difference is due, at least in part, to increased susceptibility of Fas⁺ cells in the gld mouse to undergo FasL-mediated apoptosis as they infiltrate the FasL expressing allogeneic cornea.

Keywords: transplantation • immune tolerance/privilege • immunomodulation/immunoregulation