Research Group

  • Dr. Francois Denis, Principal Investigator
  • Dr. Claude Daniel, Co-Investigator
  • Dr. Denis Girard, Co-Investigator


  • INRS-Institut Armand-Frappier, Laval, Canada


  • Creating Artificial Immunoprivilege for Allograft Acceptance

The eye, testis and placenta are termed immunoprivileged sites because they are protected from the immune system through the expression of the FasL molecule, which causes the death of infiltrating auto-reactive T cells. This permanent removal of auto-reactive T cells prevents any further attacks from the immune system and creates tolerance. While the use of immunosuppressive drugs has afforded success in organ transplantation, permanent graft acceptance is still elusive because of the phenomenon of chronic rejection. Given that inducing immunoprivilege within allografts was expected to induce tolerance, researchers have expressed FasL in grafts, but surprisingly this caused accelerated organ rejection. The cause of this acute rejection was massive neutrophilic infiltration, revealing that FasL had chemotactic properties towards neutrophils. This novel inflammatory property of FasL remains ill defined and requires molecular characterisation before the promise of immunoprivilege can be applied to organ transplantation.

This research project aims at defining the molecular determinants of FasL involved in its chemotactic and apoptotic properties. Through molecular techniques, these two properties will be dissociated, and non-chemotactic pro-apoptotic forms of FasL will be designed.

Subsequent work will attempt to target the engineered FasL molecules to grafts, through the development of high-affinity single-chain antibodies recognising donor-specific molecules. Dual-specificity molecules, consisting of FasL and single-chain antibodies, will then be constructed and tested for their potency in vitro. The efficacy of the novel reagents will be tested in vivo using a unique murine model of graft rejection that allows evaluation of two important pathways involved in graft rejection. It is anticipated that these studies will allow induction of artificial immunoprivilege and afford permanent allograft tolerance.