Fas ligand-transfected myoblasts and islet cell transplantation

Background. Expression of Fas ligand (FasL, CD95L) within the local environment of an allograft may protect from rejection by inducing apoptosis of infiltrating T cells. However, there is mounting evidence that ectopic expression of Fast stimulates an inflammatory response and targets the Fast-expressing tissue for destruction. Given the potential. therapeutic applicability of Fast-based immune protection, we sought to determine whether ectopic Fast expression was detrimental and to analyze the inflammatory response induced by ectopic Fast expression in the absence of any confounding allo-immune responses. Methods and Results. Two myoblast cell fines expressing different levels of functional FasL were produced. Co-implantation of FasL-expressing myoblasts with syngeneic islets allowed examination of the inflammatory response induced by ectopic FasL expression. In contrast to the suggested benefits of localized FasL expression, islets co-implanted with FasL-expressing myoblasts were destroyed in a vigorous inflammatory response predominated by neutrophils, Interestingly, FasL expression also had a marked antitumor effect. Conclusions. Unless FasL-dependent neutrophil-mediated inflammation can be prevented, it is unlikely that this strategy will be useful for preventing allograft rejection.