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-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.
Qin
L
L
Department of Surgery, University of Michigan, Ann Arbor 48109, USA.
Chavin
K D
KD
Ding
Y
Y
Tahara
H
H
Favaro
J P
JP
Woodward
J E
JE
Suzuki
T
T
Robbins
P D
PD
Lotze
M T
MT
Bromberg
J S
JS
D000818:Animals; D001483:Base Sequence; D002465:Cell Movement / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006082:Graft Enhancement, Immunologic; D006085:Graft Survival / Q000187:drug effects / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D016753:Interleukin-10 / Q000008:administration & dosage / Q000235:genetics* / Q000627:therapeutic use; D018655:Lymphocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008969:Molecular Sequence Data; D012190:Retroviridae / Q000235:genetics* / Q000276:immunology; D013045:Species Specificity; D013234:Stem Cells / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014184:Transplantation, Homologous; D014764:Viral Proteins / Q000235:genetics* / Q000627:therapeutic use
D014764:Viral Proteins; D016753:Interleukin-10