Abstract
Rejection of MHC-mismatched graft is the main barrier to successful transplantation. Improvement of immunosuppressive medications has allowed transplanted organs to be accepted for a longer term. However, long-term immunosuppression increases the incidence of infections and malignancy. Induction of donor-specific tolerance would avoid both chronic graft rejection and the side effects associated with chronic and nonspecific immunosuppressive therapy. This would be the ultimate goal of immunosuppression for patients undergoing organ transplantation. Numerous experimental studies have demonstrated the induction of immunotolerance in rodent models, but there are some barriers to extend those protocols to large animal models and to human clinical applications. Among these barriers, mixed chimerism induced by bone marrow transplantation is an effective therapy to induce tolerance of T cells, B cells and NK cells in both allogeneic and xenogeneic combinations.
This review will focus on how mouse studies have facilitated our understanding of the mechanisms underlying immunotolerance, and summarizes the major findings to highlight the mixed chimerism induced by bone marrow transplantation, costimulation blockade and regulatory T cells.
