Research Group

  • Prof. Megan Sykes, Applicant
  • Assist. Prof. Yufeng Shen, Co-Applicant
  • Dr Julien Zuber, Research Assistant
  • Prof. Vivette D'Agati, Collaborator
  • Prof. Bruce Levin, Collaborator
  • Assist. Prof. Waichi Wong, Collaborator
  • Assoc. Prof. Emmanuel Zorn, Collaborator

Location

  • Columbia University, New York, USA

Title

  • Tracking donor-specific lymphocytes in transplant recipients

Immunosuppressive treatments for transplants could be better tailored to the individual patient if we had a tool that accurately reflected the specific immune response to the patient's donor. T cells are the key players of the immune system in the process of rejection. Each T cell has a uniquely rearranged gene that produces a unique T cell receptor that sees its specific antigen. The large size and diversity of the donor-reactive T cell pool has to date rendered identification of this entire population impossible. We have developed a new method of identifying all T cells in the blood of an organ recipient that react to donor. A pre-transplant immune assay with blood samples from donor and recipient, combined with high-throughput DNA sequencing, enables the genetic identification of the many specifically donor-reactive T cell receptors. We are then able to track these cells post-transplantation in blood and biopsy samples. In a cohort of donor-tolerant patients induced by combining bone marrow and kidney transplantation, we have observed that post-transplant loss of donor-reactive T cells in peripheral blood more accurately correlates with outcome than any other laboratory assay. In a pilot series of 20 kidney transplant recipients, we propose to compare frequencies of donor-reactive T cells in pre-transplant and post-transplant blood and biopsies. We hypothesize that rejection will be reflected in an increased frequency of donor-reactive T cells in peripheral blood and biopsy of the transplanted organ. We will look for correlations of expansions and reductions in donor-specific T cells in the blood in association with outcomes. Our novel, non-invasive method for physically tracking donor-reactive T cells will provide new understanding of human immune responses to transplants and may ultimately provide a guide for personalized decision-making about patient treatments

Final Report