Transplantation Proceedings
Volume 36, Issue 2 , Pages 397-398, March 2004

Viral interleukin-10 gene therapy to induce tolerance to solid organ transplants in mice

  • S.K Salgar

      Affiliations

    • Department of Surgery (S.K.S., D.Y., J.M., A.G.T.), University of Miami, Miami, Fl, USA
    • Corresponding Author InformationAddress reprint requests to Shashikumar K. Salgar, PhD, Director, Liver/GI Transplantation Research Laboratory, Department of Surgery, University of Miami School of Medicine, 1450 NW 10th Avenue, Room 2012, Miami, Florida 33136, USA.
    • ,
  • D Yang

      Affiliations

    • Department of Surgery (S.K.S., D.Y., J.M., A.G.T.), University of Miami, Miami, Fl, USA
    • ,
  • P Ruiz

      Affiliations

    • Department of Pathology (P.R.), University of Miami, Miami, Fl, USA
    • ,
  • J Miller

      Affiliations

    • Department of Surgery (S.K.S., D.Y., J.M., A.G.T.), University of Miami, Miami, Fl, USA
    • ,
  • A.G Tzakis

      Affiliations

    • Department of Surgery (S.K.S., D.Y., J.M., A.G.T.), University of Miami, Miami, Fl, USA

Abstract 

In this study, a novel gene therapy approach to prolong allograft survival was designed. Autologous (syngeneic) hematopoietic stem cell–enriched bone marrow cells (HSC; lin−) engineered with the vIL-10 gene (vIL-10-HSC) were injected (4 to 6 × 106 cells, iv) into lethally (9.5 Gy) or sublethally (4 Gy) irradiated CBA/J mice 6 weeks prior to allogeneic heart (C57BL/6) transplantation (Tx). Cardiac allograft survival was significantly (P < .004) prolonged in lethally (71 ± 40 days) and sublethally (114 ± 15 days) irradiated mice that received vIL-10-HSC compared to controls that received no HSC (11 ± 1 days), unengineered HSC, or vector-DNA–engineered HSC (12 to 16 days). Tolerant graft histopathology demonstrated mild arteritis/venulitis (grade 0.7) and rejection (grade 1.0). Intragraft expression of costimulatory molecules (B7.1, B7.2), cytokines (IL-2, IL-4, mIL-10, IFN-γ), and iNOS molecules were markedly lower in tolerant grafts that survived for >100 days; recipient T lymphocytes demonstrated hyporeactivity to donor and third-party antigens in mixed lymphocyte cultures. These findings have important implications and potential therapeutic applications in transplantation and autoimmune diseases.

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PII: S0041-1345(03)01320-4

doi:10.1016/j.transproceed.2003.12.009

Transplantation Proceedings
Volume 36, Issue 2 , Pages 397-398, March 2004

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