THE COURSE OF PANCREAS ALLOGRAFTS IN RATS CONDITIONED BY SPLEEN ALLOGRAFTS1

SUMMARY A new technique for transplanting duct-ligated rat pancreas grafts, rather similar to the technique for spleen grafting in rats, is presented. Inbred AGUS and WAG rats with a strong Ag-B incompatibility were used. Duct-ligated pancreas AGUS to AGUS isografts survived indefinitely in streptozotocin-induced diabetic hosts while WAG to AGUS allografts were quickly rejected. However, when WAG spleen and pancreas were transplanted en bloc to AGUS rats, endocrine pancreas graft function persisted for up to 6 weeks. This finding of a transient protection of pancreas allografts by donor-strain spleen allografts led to further experiments. AGUS recipients first received WAG spleen allografts which then were removed after 3 to 5 months, at which time WAG pancreas allografts were inserted. Sixty-eight per cent of these grafts survived and cured their hosts of streptozotocin-induced diabetes. Partly because of disappointing clinical results in pancreas transplantation (2), and partly because of the theoretical advantages and the impressive successes with transplantation of isolated pancreatic rat islets into isogeneic diabetic recipient animals (1, 23, 26), the concept of whole organ pancreas transplantation with the objective of alleviating or curing diabetes has lost ground, judging by recent communications in this field (31). The momentum seems to have been gradually shifting toward grafting of isolated islets. They would appear, for many and obvious reasons, preferable even in the clinical situation. The major surgical problems faced by recipients of whole organ pancreas grafts, particularly the drainage of the pancreatic juice, would be absent in patients receiving islet grafts. However, such drainage problems have been avoided in beagles (16), pigs (12, 27), and rats (36, 41) receiving grafts with the pancreatic duct ligated, which did not interfere with a sufficient islet function. In man, the outcome of whole organ pancreas allografts, with or without ligation of the pancreatic duct, and of isolated islets has been disappointing so far (2, 31, 33). This poses the question as to whether vascularized pancreas allografts are more vulnerable to immunological assault than other organ grafts. It seemed interesting, therefore, to study segmental duct-ligated pancreas allografts in the same donor-recipient pairing of inbred WAG to AGUS rats, in which spontaneously surviving spleen allografts had rendered the recipient rats specifically unresponsive toward subsequent skin allografts. This state of unresponsiveness only became operative about 6 weeks after spleen grafting (4, 5, 10). Pancreas transplants in rats have been described by different groups using either grafts with ligation of the pancreatic duct (36, 41), or with drainage of the pancreatic juice (29, 30, 35, 45). No such allografts have survived without immunosuppression (30, 35, 37, 41).