SURVIVAL AND FUNCTION OF SYNGENEIC RAT ISLET GRAFTS PLACED WITHIN THETHYMUS VERSUS UNDER THE KIDNEY CAPSULE

The role of the thymus in the ongoing acquisition of tolerance to self antigens has made it an attractive site for islet transplantation. Se veral studies have reported survival of rodent islet allografts in the thymus without requiring the long-term use of immunosuppressive agent s; however, the degree of glucose homeostasis in the intrathymic islet transplant recipients has not been examined. We transplanted 500, 100 0, or 2000 syngeneic islets into the thymus of streptozotocin-induced diabetic Wistar-Furth rats, and compared the metabolic response of the se recipients with animals receiving 2000 syngeneic islets under the k idney capsule. Three of four recipients which received 2000 islets und er the kidney capsule achieved normoglycemia (less than or equal to 8. 4 mmol/L) within 1 wk and all animals became normoglycemic within 2 wk posttransplantation. In contrast, intrathymic implantation of 2000 is lets induced normoglycemia in only one of six recipients during the sa me time interval, and when this number was reduced to 1000 or 500 isle ts, none of the recipients (n = 6) normalized within 1 wk posttranspla ntation. Animals that received an intrathymic transplant were glucose intolerant compared to normal controls and animals with subcapsular is let transplant. Removal of the graft-bearing organs resulted in hyperg lycemia in all cases, and examination of the grafts revealed the prese nce of numerous well-granulated insulin-containing cells in both sites . The cellular insulin content of the subcapsular grafts (67.4 +/- 12. 1 mu g; n = 4) was significantly higher (p less than or equal to 0.05) than what was extracted from intrathymic grafts (9.5 +/- 1.2 mu g fro m 1000 islets; n = 3 and 20.0 +/- 4 6 mu g from 2000 islets; n = 3) We conclude that 2000 syngeneic islets implanted either in the thymus or beneath the kidney capsule can normalize hyperglycemia in streptozoto cin-diabetic rats; however, normal glucose tolerance was not establish ed in intrathymic islet recipients, suggesting that a higher number of islets may be necessary to achieve normal glucose homeostasis. (C) 19 97 Elsevier Science Inc.