Better understanding of rejection after organ transplantation

Abstract

Solid organ transplantation (SOT) and allogeneic hematopoietic stem cell transplantation (HSCT) are the only curative approaches for patients with organ failure or certain high-risk hematological malignancies, respectively. Graft rejection, graft-versus-host disease (GVHD), and disease recurrence are the major complications of these treatments and are important in affecting the overall outcome of patients with the transplant. Graft rejection and GVHD are mediated by host and donor T lymphocytes, respectively. The graft-versus-leukemia (GVL) effect is also mediated by donor T lymphocytes targeting leukemic cells and is correlated inversely with relapse. Therefore, to obtain a better insight into graft injury and rejection in SOT as well as the interplay between GVHD and GVL in HSCT, better understanding of the recipient immune reaction against transplanted organs and donor T-cell reconstitution and function is essential. Next-generation sequencing approaches to comprehensively characterize the TCR repertoires in patients undergoing SOT or HSCT are becoming readily available. Such approaches provide valuable, comprehensive longitudinal analyses that define the kinetics of each TCRalpha and -beta clone and the changes in the diversity of CDR3. They also allow for identification of the expanded T-cell clones that are possibly associated with the disease conditions and clinical outcome.