Retrovirus-mediated transfer of viral IL-10 gene prolongs murine cardiac allograft survival

Lihui Qin, Kenneth D. Chavin, Yaozhong Ding, Hideaki Tahara, Justin P. Favaro, Jennifer E. Woodward, Tadamichi Suzuki, Paul D. Robbins, Michael T. Lotze, Jonathan S. Bromberg

Research output: Contribution to journalArticlepeer-review

175 Scopus citations

Abstract

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-mediated 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 was specific, dose dependent, and restricted to the site of transplantation. 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 cytotoxic T cells and IL-2-producing helper T cells. Thus, the transient local expression of a gene encoding an immunosuppressive protein within a graft can generate local immunosuppression, making gene therapy a viable approach for facilitating transplantation.

Original languageEnglish (US)
Pages (from-to)2316-2323
Number of pages8
JournalJournal of Immunology
Volume156
Issue number6
StatePublished - Mar 15 1996

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