Research Group

  • Dr Anatolij Horuzsko, Principal Investigator


  • Medical College of Georgia, Augusta, USA


  • Improvement of Allograft Survival by Special Forms of HLA-G and Inhibitory Receptor

A key factor driving the chronic rejection in clinical transplantation is persistent T cell-mediated alloimmune response. Therefore, the development of novel therapeutic strategies to target T cell alloimmune response would appear to be an important direction in the prevention and management of chronic rejection. In view of the role of immune mechanisms in chronic allograft loss, establishment of immunological tolerance is of great interest. The successful semiallogeneic pregnancy is the natural model where multiple mechanisms underlie maternal tolerance of genetically different fetal tissues during pregnancy. The key player in this process is HLA-G, a unique novel gene that remains as antigen of great interest and a focus of experimental evaluation. One of the major roles suggested for the HLA-G protein was the inhibition of function of T cells and dendritic cells via inhibitory receptors. We have identified a novel model of immunomodulation where the defect of T cell responses has been mediated by special forms of HLA-G via interaction with inhibitory receptors. The biological significance of the proposed study is to determine the mechanisms of the tolerogenic function of different isoforms of HLA-G and transfer this knowledge to improve allogeneic tissue and organ graft survival. These discoveries will permit the development of new therapeutic strategies that specifically target molecules involved in the immune tolerance. They form the basis for further studies on the critical role of HLA-G molecules in the interaction with inhibitory receptors in clinical organ transplantation, when both HLA-G and its receptors are expressed. An understanding of the mechanisms of the alteration of immunocompetent cell function by HLA-G and its inhibitory receptors will allow us and others to generate genetically engineered and highly purified tolerogenic cells, regulatory cells to induce and control the antigen-specific tolerance for therapy for transplant rejection, autoimmune disease, or allergy.

Final Report