Role of indirect allorecognition in allograft rejection.

It is now clear from animal studies that indirect allorecognition occurs during allograft rejection and that this pathway plays a role in mediating the rejection process. Whether this pathway is the dominant pathway responsible for chronic rejection remains to be established, but this is an intriguing hypothesis that may have major implications for development of novel therapies for this disorder. In addition, there are data to indicate that indirect allorecognition may play a role in maintenance of allograft acceptance, and that provision of appropriate MHC peptides via different routes can result in potent degrees of specific allo-tolerance. Expanded experimentation in animals and in humans is therefore in order; first, to dissect more closely the molecular basis of allorecognition and establish the role of the indirect pathway in acute versus chronic rejection, and second to utilize the immunomodulatory properties of MHC peptides or other novel strategies which targets indirect allorecognition in promoting graft acceptance.