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

Academic Article
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Overview

authors

  • Qin, L. H.
  • Chavin, K. D.
  • Ding, Y. Z.
  • Tahara, H.
  • Favaro, J. P.
  • Woodward, J. E.
  • Suzuki, T.
  • Robbins, Paul D.
  • Lotze, M. T.
  • Bromberg, J. S.

publication date

  • March 1996

journal

  • Journal of Immunology  Journal

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.

subject areas

  • Animals
  • 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
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Identity

International Standard Serial Number (ISSN)

  • 0022-1767

PubMed ID

  • 8690923
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Additional Document Info

start page

  • 2316

end page

  • 2323

volume

  • 156

issue

  • 6

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