Regulation of transplantation tolerance by antigen-presenting cells

The induction of antigen-specific tolerance remains the Holy Grail of transplant researchers. The alternative approach, using a spectrum of nonspecific immunosuppressive drugs and/or other regimens, although proving sufficiently successful to propel transplantation upward as the treatment of choice in many cases for end-organ failure, is still fraught with complications. These include malignancy, infection, and treatment toxicity, which are hoped to be avoided in scenarios of specific tolerance. The review below summarizes our current state of knowledge concerning manipulations aimed at altering the manner in which foreign antigen is “seen” by the immune system, as one approach to the induction of transplantation tolerance. As will become evident, remarkable progress has been made in defining the myriad of interactions that result in optimal lymphocyte triggering for graft rejection and the regulation of that activation by the host immune system. Although, to date, no protocol has been developed for routine application in clinical situations, it seems that there is indeed now hope.