Research Group

  • Prof. Nuala Mooney, Principal Investigator
  • Prof. Danis Glotz, Research Associate
  • PhD Béatrice Charreau, Research Associate
  • MD Cécile Taflin, Collaborator
  • PhD Benoit Favier, Collaborator
  • Dr Alain Haziot, Collaborator
  • PhD Catherine Gelin. Research Assistant
  • Prof. Marie-Noelle Peraldi, Collaborator
  • Dr Jeanning Berrou, Research Assistant
  • Mr Alain Savenay, Technician


  • INSERM, Paris, France


  • Regulation of Endothelial Cell Allogenicity by HLA Class II Alloantibodies

Objectives: The aim of this project is to understand the mechanisms leading to the widely documented noxious effect of HLA-DR donor-specific antibodies on graft survival after renal transplantation. Recent data indicate that the most accurate marker of graft destruction is the combination of HLA alloantibodies and activated endothelial cells. Human microvascular cells express HLA-DR under conditions of inflammation, and our recent studies show that they induce allogenic proliferation and polarisation of CD4+ T lymphocytes towards inflammatory and regulatory sub-populations. We will address the question of how the presence of HLA-DR antibodies effects the endothelial cell mediated CD4+-T lymphocyte polarisation in response to HLA-DR expressing endothelial cells and the mechanism involved. We have identified the role of the cytokine environment and of STAT-3 in inducing the inflammatory CD4+ T lymphocyte response and the implication of endothelial cell expression of CD54 in inducing the regulatory response.
Expected results: Our preliminary data show that the human endothelial cells induce allogenic T-lymphocyte proliferation under inflammation conditions. In this project we will examine the ability of HLA-DR antibodies to modify the allogenic response, either in terms of T lymphocyte proliferation or T lymphocyte polarisation towards an inflammatory response (Th17 or Th1) or towards an allosuppressive regulatory profile (FoxP3hi, CD25hi, CD4+). The identity of the proteins expressed by the endothelial cell which orient the response towards either inflammation or suppression will be determined. In addition, we will assess the capacity of identified actors in these responses (CD54, P-SAT-3 and IL-6) to be used as diagnostic markers and/or therapeutic targets using patient material obtained from protocol biopsies. A working collaboration with the Department of Nephrology on the site has been established.