RESIDENT RESEARCH AWARD - TRANSDUCTION OF HEPATIC ALLOGRAFTS ACHIEVESLOCAL-LEVELS OF VIRAL IL-10 WHICH SUPPRESS ALLOREACTIVITY IN-VITRO

The application of gene therapy in transplantation might be targeted a t immunoregulation within the donor graft. Viral IL-10 (vIL-10) down-r egulates antigen presenting cells (APC) and effector functions in in v itro and in vivo models of alloreactivity. In the current study, we ha ve constructed a replication-defective adenovirus bearing the cDNA enc oding viral IL-10 and examined the level and chronicity of its express ion in rat liver allografts up to 7 days after orthotopic transplantat ion. The results demonstrate that liver allografts may be efficiently transfected with adenovirus expressing viral IL-10. Detection of the r ecombinant viral cytokine was limited to the allograft without measura ble levels in peripheral blood. In parallel, the effect of vIL-10 on m ixed leukocyte reaction is also assessed using peripheral blood lympho cytes obtained from naive donor and recipient animals. Equivalent leve ls of viral IL-10 (5-10 ng/ml) achieved after adenovirus-mediated gene transfer suppress the in vitro alloreactivity of peripheral blood lym phocytes up to 70%. Adenovirus-mediated gene transfer of viral IL-10 o ffers the promise of effectively and favorably altering the alloreacti ve immune response. (C) 1995 Academic Press, Inc.