- Dr. Benoît Salomon, Principal Investigator
- Dr. José Cohen, Co-Investigator
- Aurélie Trenado, Research Associate
- Dr. Sylvain Fisson, Research Associate
- Dr, Benoît Barrou, Research Associate
- Dr. Frédéric Charlotte, Research Associate
- Hôpital de la Pitié Salpêtrière, Paris, France
- Prevention of Allograft Rejection by Specific Tolerance Induction Using CD4+ CD25+ Regulatory T Cells
and goal of our research
Solid organ transplantation necessitates the administration of non-specific immunosuppressive treatments. In some patients, these only imperfectly prevent graft rejection and can have severe side effects. Alternative treatments that induce specific tolerance to the graft are thus desirable. The goal of our project is to test this possibility by using a population of immunoregulatory CD4+CD25+ T cells (Treg) that we and others have shown to be involved in the regulation of auto-immune diseases and graft-versus-host disease.
can our goal be reached?
After transplantation, alloantigens (histocompatibility antigens) from the graft are presented either by donor (direct pathway) or recipient (indirect pathway) antigen- presenting cells. Indirect evidence suggests that prevention of allograft rejection by Treg may be achieved by using cells previously selected to recognize specifically donor-type alloantigens through the direct and/or indirect pathways. In preliminary experiments, we were able to expand and select in vitro Treg specific for alloantigens presented by the direct pathway that function in vivo to induce specific tolerance. In our research proposal, we will optimize this culture and set up new conditions for the generation of Treg specific for alloantigens presented by the indirect pathway. These two types of Treg will then be tested in parallel for their ability to control allograft rejection in mouse models of skin and islet transplantation. All these culture conditions should be transferable to the human setting. Thus, we will adapt the protocol for in vitro selection of alloantigen-specific Treg in humans.
impact of our research in medicine
The generation of alloantigen-specific Treg may be used in the future in organ transplantation to induce long-term acceptance of the graft. This new therapeutic strategy may allow a reduction in the doses of the immunosuppressive drugs, thus limiting adverse events.