Research Group

  • Prof. Reginald Gorczynski, Principal Investigator
  • Dr. Gary Levy, Co-Investigator


  • University Health Network, Toronto, Canada


  • Interaction of OX2 with its Receptor Controls Organ Rejection

Induction of immunological tolerance is important for promoting long-term organ and/or tissue graft acceptance. Our investigations have shown that tolerance to renal allografts in mice/rats followed after infusion of donor cells into the liver (via the portal vein), and that this was associated with increased expression by recipient cells of a novel molecule, OX2, which was crucial for tolerance induction. As “proof of principle” for this hypothesis, we showed that antibodies to OX2 blocked tolerance to renal allografts, while a soluble form of OX2 could induce tolerance in rodents. Our institution is currently engaged in testing these reagents in a large animal transplant model, with a view to phase 1 clinical trials in the future.

The biochemistry of OX2 suggested that it only delivers a tolerance signal following engagement of its receptor (OX2R). We have prepared antibodies to OX2R, and in addition are making a soluble form of OX2R. We propose to test the hypothesis that OX2R itself provides a key signal for tolerance induction in transplantation by using anti-OX2R to induce tolerance (and soluble OX2R to block that induction).

Other experiments in our laboratory are involved in the generation of transgenic mice that overexpress the OX2 molecule on all tissues (OX2tg/tg), and mice in which the gene encoding the receptor has been genetically deleted (OX2R KO). A group at DNAX Research Institute has already created an OX2 KO mouse, and showed that it has susceptibility to autoimmune disease. We predict that transplants will be unsuccessful in OX2 KO mice, unless organs are used from OX2tg/tg. Transplants in OX2R KO mice will not be accepted, even from OX2tg/tg mice.

These studies from animal transplant models will provide information on immunoregulation applicable to numerous human diseases, including transplantation, allergy and autoimmunity.