Fas ligand-transfected myoblasts and islet cell transplantation

Background. Expression of Fas ligand (FasL, CD95L) within the local environ ment of an allograft may protect from rejection by inducing apoptosis of in filtrating T cells. However, there is mounting evidence that ectopic expres sion of Fast stimulates an inflammatory response and targets the Fast-expre ssing tissue for destruction. Given the potential. therapeutic applicabilit y of Fast-based immune protection, we sought to determine whether ectopic F ast expression was detrimental and to analyze the inflammatory response ind uced by ectopic Fast expression in the absence of any confounding allo-immu ne responses. Methods and Results. Two myoblast cell fines expressing different levels of functional FasL were produced. Co-implantation of FasL-expressing myoblast s with syngeneic islets allowed examination of the inflammatory response in duced by ectopic FasL expression. In contrast to the suggested benefits of localized FasL expression, islets co-implanted with FasL-expressing myoblas ts were destroyed in a vigorous inflammatory response predominated by neutr ophils, 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.