RETROVIRUS-MEDIATED TRANSFER OF VIRAL IL-10 GENE PROLONGS MURINE CARDIAC ALLOGRAFT SURVIVAL

A murine heterotopic, nonvascularized cardiac allograft model was used to examine the effects of the immunosuppressive cytokine, viral IL-10 (vIL-10), delivered by gene transfer on graft rejection, Retroviral-m ediated gene transfer and expression of vIL-10 significantly prolonged allograft survival, without conventional systemic immunosuppression, from 12.1 +/- 0.8 days to 39.4 +/- 2.5 days (p < 0.0001), The effect w as specific, dose dependent, and restricted to the site of transplanta tion, PCR analysis demonstrated specific expression of the transferred gene within the allograft, Analysis of the cellular infiltrate in the allografts showed a reduction in T cells and alloantigen-specific cyt otoxic T cells and IL-2-producing helper T cells, Thus, the transient local expression of a gene encoding an immunosuppressive protein withi n a graft can generate local immunosuppression, making gene therapy a viable approach for facilitating transplantation.