Fas ligand gene transfer to renal allografts in rats: effects on allograft survival

Transplantation. 1998 Jan 27;65(2):155-60. doi: 10.1097/00007890-199801270-00002.


Background: Fas ligand (FasL) induces apoptosis of cells bearing its receptor Fas, and has been shown to be important in T-cell development and regulation and in immune privilege. We hypothesized that FasL expression by renal allografts might provide protection from rejection.

Methods: The murine FasL cDNA was cloned into a replication-defective adenovirus (AdV-FasL). Protein expression was confirmed by immunostaining of AdV-FasL-transduced HeLa cells. Allogeneic kidney transplants were performed between WF (RT1u) donors and Lewis (RT1) recipients. Donor kidneys were perfused in situ with saline alone (control), or 9 x 10(9) plaque-forming units of AdV-FasL. One native kidney was removed at the time of transplant and the other at 6 or 7 days. Uremic death was the endpoint, and deaths within 7 days of transplant were excluded. Transduced allografts were stained for FasL expression using a monoclonal antibody and tested for FasL mRNA production by reverse transcriptase-polymerase chain reaction and Northern blotting.

Results: Immunostaining of AdV-FasL-transduced allografts demonstrated efficient gene transfer lasting approximately 2 weeks, and FasL mRNA production in the AdV-FasL-transduced allografts was confirmed by Northern blotting and reverse transcriptase-polymerase chain reaction. Mean survival of animals with AdV-FasL-transduced renal allografts was 27.8 days vs. 11.6 days in control animals (P < 0.05).

Conclusions: (1) Adenoviral vectors can successfully transduce rat kidneys with the FasL cDNA. (2) FasL gene transfer prolongs rat renal allograft survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae
  • Animals
  • Cytotoxicity, Immunologic* / genetics
  • DNA, Complementary
  • Fas Ligand Protein
  • Gene Transfer Techniques
  • Graft Rejection / immunology
  • Graft Rejection / metabolism*
  • Graft Rejection / prevention & control
  • Graft Survival* / genetics
  • Graft Survival* / immunology
  • HeLa Cells
  • Humans
  • Immunohistochemistry
  • Kidney Transplantation / immunology*
  • Kidney Transplantation / pathology
  • Membrane Glycoproteins* / genetics
  • Membrane Glycoproteins* / immunology
  • Membrane Glycoproteins* / metabolism
  • Polymerase Chain Reaction
  • RNA, Messenger / analysis
  • Rats
  • Rats, Inbred Lew
  • Rats, Inbred WF
  • Transduction, Genetic
  • Transplantation, Homologous / immunology*
  • Transplantation, Homologous / pathology


  • DNA, Complementary
  • FASLG protein, human
  • Fas Ligand Protein
  • Faslg protein, rat
  • Membrane Glycoproteins
  • RNA, Messenger