Research Group

  • Dr. Régis Josien, Principal Investigator
  • Dr. Cristina Cuturi, Co-Investigator
  • Prof. Jean-Paul Soulillou, Co-Investigator
  • Cécile Voisine, Research Assistant
  • Dr. Patrick Mathieu, Research Assistant
  • Dr. Yongwon Choi, Consultant


  • ITERT/ INSERM Unit 437, Nantes, France


  • The Role of TRANCE during Allograft Rejection and Tolerance

The understanding of immune mechanisms leading to allograft rejection and allograft tolerance is an important step toward the identification of molecular targets of current and new immunosuppressive drugs. Recent results have shown that the molecule CD40 ligand (CD40L) which is expressed on activated CD4+ T lymphocytes and its counter-receptor CD40 which is expressed on antigen presenting cells (dendritic cells, macrophages, B lymphocytes) represented a major pathway for T cell activation both in vitro and in vivo. Monoclonal antibodies that antagonize CD40L have been shown to delay allograft rejection in rodent and monkey models and will probably be used in the future in human organ transplantation. Recently, a new member of the tumor necrosis factor (TNF) family, called TRANCE (TNF- related activation induced cytokine), has been described. This molecule shares functional properties with CD40L but appears to be more specialized in the interaction between T cells and dendritic cells, two cell subsets which play a pivotal role in immune responses to allografts. In vivo studies suggest that, in the absence of the CD40L/CD40 pathway, the immune system can use the TRANCE-TRANCE-receptor pathway to activate T helper cells. In this proposal, we will analyze the role of TRANCE/TRANCE-receptor interactions during immune responses leading to allograft rejection and allograft tolerance using a rat model of heart allograft. The expression of TRANCE and its receptor will be assessed in allografts and lymphoid organs. TRANCE-blocking bioreagents will be used in vivo and will allow us to determine the role of this pathway in experimental allograft rejection and tolerance. Based on these studies and their results, we will design new experiments to test the effects of TRANCE-blocking bioreagents in a monkey model of renal allograft.