Prevention of rejection by treatment of the graft: an overview.

Two signals are required for T cell activation, and because of this transplantation antigen, of itself, is not the major barrier to grafting. The major stimulus for the rejection response come from active antigen presentation by donor APC's. It is possible to reduce allograft immunogenicity by removal of these cells from the graft prior to transplantation. This procedure has been shown to be effective in the case of thyroid, parathyroid, and islet cell transplantation in animals and in the case of parathyroid grafting in man. The cultured graft is in a metastable state in the immediate post-transplantation phase; such grafts are rejected by either active or passive immunization of the host animal. With the passage of time the metastable graft moves into a stable relationship with the host. This change is the result of tolerance induction in the adult animal. The fact that allografting can be carried out without a requirement for recipient immunosuppression suggests that the helper pathway involving processing of graft antigen and presentation on host APC's, is relatively inefficient in vivo. Experimentally, lymphokine provided by T cell triggering in the region of the metastable graft does not lead to the generation of systemic immunity, suggesting that there are much more stringent requirements for the expression of T helper function in vivo than in vitro.