The role of adaptation in allograft acceptance.

The experimental and clinical data suggest that both a decrease of antigen expression and decreased perfusion can protect against immunologically mediated destructive processes. In the adaptation of skin grafts, these factors could be interrelated. Inadequate perfusion might lead to a decreased delivery of substances that stimulate MHC antigen expression. This course of events also could explain the protection in the patient presented here. Immune deposits were completely absent in the protected segment of the kidney, although immune deposits were abundantly present in the remaining part of the kidney, and circulating anti-donor antibodies were demonstrable after the transplanted kidney had been removed. The limited availability of frozen biopsy material has prevented us from comparing the expression of MHC antigens in both kidney segments using monoclonal antibodies. But such studies might be done in experimental kidney transplants with an artificially induced stenosis of the renal artery. Except when an arterial stenosis is present, we have little reason to assume that perfusion gradually decreases in longstanding kidney grafts as it does in skin grafts. Therefore, if adaptation plays a role in the gradual decrease of the sensitivity to rejection in longstanding kidney grafts, this phenomenon must be attributed to a decreased expression of target antigens as a consequence of factors other than decreased perfusion. The most likely candidates are the immunosuppressive drugs, such as cyclosporine and prednisone, which decrease MHC antigen expression. Let me conclude by returning to my main theme of graft adaptation. It seems appropriate to end this review with a quotation from one of Woodruff's original publications on this subject: "If the phenomenon [adaptation] applies to homotransplants of normal tissues to sites other than the eye, I think it almost certain that the clinical homograft problem will be solved; if it does not, the problem may prove insoluble" [9]. Although our insight into the rejection process has increased considerably, we still do not know which factors are most important in determining the long-term survival of primarily vascularized grafts.