Morphological findings in duct-ligated pancreas grafts in the rat. An analysis of isografts, allografts, and long-standing allografts in hosts conditioned by previous spleen allograft

Abstract

The morphological findings of duct-ligated pancreas grafts in streptozotocin-induced diabetic hosts were studied using inbred AGUS and WAG rats with a major histocompatibility complex differences. AGUS to AGUS pancreas isografts survived indefinitely. Morphologically, islet tissue was partly dispersed and showed about 75% granulated beta cells. Fibrosis was minimal and inflammatory cells generally absent. WAG to AGUS allografts were quickly rejected and showed severe pancreatitis with a polymorphonuclear and mononuclear infiltrate. Islet destruction lagged behind that of exocrine tissue and vascular thrombosis was a late event. In the last group, AGUS recipients first received WAG spleen allografts which survived spontaneously. There to 5 months later they were removed and WAG pancreas allografts inserted. Sixty-eight percent of these pancreas allografts survived. Four to 10 months later they were characterized by severe dense fibrosis surrounding islet tissue. Capillaries were always present between islet cells, about 75% of which showed beta granules. A mild to moderate mononuclear cell infiltrate and vascular intimal proliferation were also part of the picture. We conclude that pancreatitis after duct-ligated pancreas allografts is not a sequel of duct ligation but results from rejection and can be prevented with adequate immunosuppression. Fibrosis does not have a detrimental effect on islet cell function as a result of the feasibility of insulin secretion by beta cells into adjacent capillaries and thence to larger vessels traversing through the dense fibrosis.