Research Group

  • Dr. Maria-Luisa Alegre, Principal Investigator
  • Dr. J. Richard Thistlethwaite, Research Associate
  • Dr. Ping Zhou, Research Associate


  • University of Chicago, Chicago, USA


  • Role of Costimulatory Molecules in Cardiac Allograft Rejection

T lymphocytes are essential for acute rejection of transplanted organs, and rejection does not occur in the absence of T cells. T cells become stimulated following encounter with antigen (including transplant antigens) by signals delivered by the T cell receptor during antigen recognition together with signals delivered by costimulatory molecules expressed on T cells. Transplant antigens are recognized by T cells either on the graft itself, or on the surface of antigen-presenting cells that also express the ligands for the T cell costimulatory molecules. However, the actual mechanism of rejection is not well understood. For example, neither the type of antigen-presenting cell nor its origin (the transplant recipient or the graft) is clearly defined. In addition, it is not known whether T cells participate in the destruction of the graft, or if they activate other effector cells that reject the transplant.

The availability of mice made genetically deficient in specific costimulatory molecules, costimulatory ligands or signaling pathways has provided tools to dissect the role of these individual molecules in the promotion or prevention of graft rejection. We have recently shown that T cells from recipient mice preferentially receive specific costimulatory signals from host than from graft antigen-presenting cells. The aims of this study are to characterize the cell types utilized for costimulation and antigen presentation to T cells and the mechanism of rejection operating in mice with defective costimulation capacity. Immunosuppressive regimens currently in use in clinical transplantation induce a global immunosuppression of all T cells, which results in increased susceptibility to infections and cancers. This study may reveal the importance of alternative costimulatory molecules. This has the potential to help design better immunosuppressive regimens applicable to the clinical setting with the ultimate goal of achieving donor-specific tolerance.