Transduction of hepatic allografts achieves local levels of viral IL-10 which suppress alloreactivity in vitro.
The application of gene therapy in transplantation might be targeted at immunoregulation within the donor graft. Viral IL-10 (vIL-10) down-regulates antigen presenting cells (APC) and effector functions in in vitro and in vivo models of alloreactivity. In the current study, we have constructed a replication-defective adenovirus bearing the cDNA encoding viral IL-10 and examined the level and chronicity of its expression in rat liver allografts up to 7 days after orthotopic transplantation. The results demonstrate that liver allografts may be efficiently transfected with adenovirus expressing viral IL-10. Detection of the recombinant viral cytokine was limited to the allograft without measurable levels in peripheral blood. In parallel, the effect of vIL-10 on mixed leukocyte reaction is also assessed using peripheral blood lymphocytes obtained from naive donor and recipient animals. Equivalent levels of viral IL-10 (5-10 ng/ml) achieved after adenovirus-mediated gene transfer suppress the in vitro alloreactivity of peripheral blood lymphocytes up to 70%. Adenovirus-mediated gene transfer of viral IL-10 offers the promise of effectively and favorably altering the alloreactive immune response.
Drazan
K E
KE
Department of Surgery, UCLA School of Medicine 90024-6904, USA.
Wu
L
L
Olthoff
K M
KM
Jurim
O
O
Busuttil
R W
RW
Shaked
A
A
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics*; D008099:Liver / Q000378:metabolism*; D016031:Liver Transplantation / Q000276:immunology*; D008297:Male; D008969:Molecular Sequence Data; D051381:Rats; D011912:Rats, Inbred ACI; D011917:Rats, Inbred Lew; D014184:Transplantation, Homologous
D016753:Interleukin-10