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

TitleRetrovirus-mediated transfer of viral IL-10 gene prolongs murine cardiac allograft survival.
Publication TypeJournal Article
Year of Publication1996
AuthorsQin L, Chavin KD, Ding Y, Tahara H, Favaro JP, Woodward JE, Suzuki T, Robbins PD, Lotze MT, Bromberg JS
JournalJ Immunol
Date Published1996 Mar 15
KeywordsAnimals, Base Sequence, Cell Movement, Dose-Response Relationship, Immunologic, Female, Gene Transfer Techniques, Genetic Vectors, Graft Enhancement, Immunologic, Graft Survival, Heart Transplantation, Humans, Interleukin-10, Lymphocyte Count, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Inbred CBA, Molecular Sequence Data, Retroviridae, Species Specificity, Stem Cells, T-Lymphocytes, Cytotoxic, Transplantation, Homologous, Viral Proteins

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.

Alternate JournalJ Immunol
PubMed ID8690923
Grant ListAI32655 / AI / NIAID NIH HHS / United States
DK44935 / DK / NIDDK NIH HHS / United States
P60-AR20557 / AR / NIAMS NIH HHS / United States
Related Faculty: 
Lihui Qin, M.D., Ph.D.

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