Study of the mechanisms of tolerance to primarily vascularized renal allografts in miniature swine

Transplantation of a vascularized allograft in a host leads to acute rejection of the graft and elimination of the foreign antigen. This rejection process can be avoided by inhibition of the immune response. There are different ways in which one can overcome the immune response to an allotransplant: matching, nonspecific immunosuppression and specific transplantation tolerance. The matching is based on the fact that allotransplants are rejected because the recipient’s immune system recognizes on donor cells histocompatible antigens that are different from his own. If there are no such disparate antigens, such as in identical twins, then no rejection response occurs. The most important histocompatibility antigens are those of the Major Histocompatibility Complex (MHC); known in human beings as the Human Leukocyte Antigen (HLA) system. However, there are numerous other antigens capable of causing rejection, termed minor histocompatibility antigens. Matching to avoid or eliminate the immune response in conceivable in kidney or bone marrow transplants, since the time necessary to carry out tissue typing is available. Matching, however, is unrealistic in case of liver, heart or lung transplants, since the admissible ischemia time does not allow the achievement of tissue typing. The use of nonspecific immunosuppressive drugs represents the most practical means to avoid rejection. This therapy is accountable for the enormous success in the field of transplantation over the past three decades. Such a drug regimen, however, can produce major complications during the early as well as long-term follow-up such as infections, malignancies or drug-induced side-effects. Long term, the immunosuppressive regimen therefore may directly cause loss of patients ad cannot prevent chronic rejection, which is the second major cause of graft loss. Therefore, induction of specific transplantation tolerance still represents a major goal of modern transplantation immunology. Specific
Thèse d'agrégation de l'enseignement supérieur (Faculté de médecine) -- UCL, 1995