ADENOVIRUS-MEDIATED EXPRESSION OF FAS LIGAND INDUCES HEPATIC APOPTOSIS AFTER SYSTEMIC ADMINISTRATION AND APOPTOSIS OF EX VIVO-INFECTED PANCREATIC-ISLET ALLOGRAFTS AND ISOGRAFTS

Fas ligand (FasL) mediates apoptosis of Fas-bearing cells and is expre ssed on a limited number of tissues, predominantly activated T lymphoc ytes, We describe the construction and biological activity of a replic ation-deficient type-5 adenovirus encoding murine Fast under the contr ol of the cytomegalovirus (CMV) promoter (adCMV-FasL). In vitro, Jurka t cells undergo apoptosis when co-incubated with adCMV-FasL-infected C OS cells, Systemic administration of adCMV-FasL to Wistar rats or DBA/ 2J mice results in widespread hepatic apoptosis and death in a dose-de pendent manner within 72 hr, an effect not seen in lpr mice, or animal s administered equivalent doses of adCMV-beta gal. Murine pancreatic i slets also undergo apoptosis when infected ex vivo with adCMV-FasL, re sulting in uniform primary nonfunction when transplanted into syngenei c or allogeneic diabetic recipients, These results indicate that adCMV -FasL is a potentially useful tool to study Fas/FasL biology.