Research Group

  • Dr Reza Abdi, Principal Investigator
  • Dr Tanaka Katsunori, Research Fellow


  • Brigham and Women's Hospital, Boston, USA


  • The Role of Donor Dendritic Cells in Promotion of Tolerance

To reject a graft, donor antigen should be presented by dendritic cells (DC) to recipient T cells. Consequently, recipient T cells become activated and destroy the graft. All transplanted organs contain resident DC (donor DC). Two types of pathways exist in which antigens are presented to T cells. In the direct pathway, donors DC (dDC) leave the tissue and stimulate recipient T cells. In the indirect pathway, recipient DC (rDC) uptake antigens and migrate to the peripheral lymph node where they then stimulate recipient T cells. The interaction between DC and T cells requires proper DC trafficking. This interaction requires proper cell positioning, which is fully governed by chemokines. Chemokines are inflammatory molecules secreted by almost all cells. We were the first to show the prolongation of islet allograft survival by targeting the chemokine system. Here, we would like to explore how chemokines control the maturation and migration of DC to regulate the alloimmune response. Our overall hypothesis is that targeting specific chemokine receptors important in the function of rDC and dDC in the donor tissue will achieve a more robust prolongation of heart allograft survival. This proposal consists of three aims, which are based on our preliminary data. Firstly, to characterize dDC trafficking as well as their survival in vivo post-transplantation. Secondly, we plan to study ischemia-induced dDC activity in vivo. Thirdly, we would like to manipulate the donor chemokines responsible for the generation of tissue DC (dDC). Of note, when these tissues are transplanted, they will be protected against rejection as they contain fewer DC. We believe results of these studies will elucidate the specific mechanisms leading to heart allograft rejection and will establish novel and safer anti-rejection strategies.

Progress Report
Final Report