Modulation of immunosuppression by DNA transfer in transplantation

Acute and chronic rejection of organ transplants continues to be the single most important source of allograft loss, and the induction of chronic immunosuppression leads to significant morbidity and mortality in transplants with long-term allograft function. Thus, induction of donor-specific unresponsiveness to organ allografts remains an elusive goal in clinical transplantation. Successful clinical transplantation depends upon a complex variety of factors. Such factors include the compatibility between the immunogenetic markers of the donor-recipient pairs, particularly the HLA antigens; the balance between the immunoregulatory mediators including cytokines and growth factors; and the adequacy of immunosuppression. Despite the availability of powerful immunosuppressive drugs, allograft survival remains imperfect, and long-term therapy has often been accompanied by numerous side effects. Because the ultimate goal of transplant immunology is the development of a state of nonresponsiveness to the transplanted organ, gene transfer approaches may provide useful strategies for fulfillment of this goal.