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The Journal of Immunology, Vol 156, Issue 6 2316-2323, Copyright © 1996 by American Association of Immunologists

ARTICLES

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

L Qin, KD Chavin, Y Ding, H Tahara, JP Favaro, JE Woodward, T Suzuki, PD Robbins, MT Lotze and JS Bromberg
Department of Surgery, University of Michigan, Ann Arbor 48109, USA.

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.


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