Fetal islet xenotransplantation in rodents and primates

beta cell replacement in IDDM by transplantation of either isolated adult i slets of Langerhans or of proliferating immature islet tissue from fetal pa ncreas are potential ways of curing this disease. Because of the dearth of human cadaver donors adult allogeneic islets are scarce and in most Western societies availability of human fetal tissue of suitable maturity is also uncommon. The use of xenogeneic islets from domestic species already widely used for human consumption, e.g. pigs, could overcome this scarcity but xe nogeneic tissues are faced with major problems of graft rejection. Hyperacu te rejection (HAR) is the main cause of destruction of immediately vascular ised xenografts and is caused by the interaction of natural cross-reactive antibodies with donor endothelial cells. Neovascularized islet grafts do no t have donor EC as the target for HAR and are not subjected to this problem but are still acutely rejected. The mechanism of this destruction is still poorly understood but is clearly T cell dependent. However, current immuno suppression that is usually adequate for control of allograft rejection gen erally does not prevent xenograft rejection. A better understanding of the ways in which xenoantigens are recognised and of the nature of the immune r esponse they initiate is fundamental to the development of appropriate stra tegies for the safe and effective control of xenograft rejection. The studi es summarized herein describe the response of mice and primates to a challe nge with fetal pig pancreas grafts, The rejection response that develops is different from that seen against a challenge with fetal allogeneic islets. Although the xenograft response is highly T cell dependent the actual effe cters of graft damage appear to be different from those that provoke allogr aft destruction and include macrophages and granulocytes, particularly eosi nophils, and possibly non-classical T cells.