Evaluation of intrathymic islet transplantation in the prediabetic period.

BACKGROUND: Beta-cell destruction in type I diabetes mellitus results from a chronic autoimmune process. Exposure of thymic T cells to islet antigens during the prehyperglycemic phase of diabetes may alter the likelihood of autoimmune damage to beta cells in the native pancreas. Thus we evaluated whether prophylactic major histocompatibility complex (MHC)-incompatible intrathymic islet allografts could prevent hyperglycemia and native pancreatic beta-cell destruction.

METHODS: At 4 to 6 weeks of age, diabetes-prone BioBreeding rats received intrathymic injection of 1500 to 2000 noncultured MHC-incompatible Lewis islets. No immunosuppression was administered. Age-matched littermates underwent intrathymic injection of saline solution.

RESULTS: None of 13 BioBreeding rat recipients of prophylactic intrathymic Lewis islet allografts became hyperglycemic versus 13 of 13 control rats (p less than 0.001). The age at onset of diabetes in the control group ranged from 77 to 104 days (mean, 86 days). Normoglycemia in recipients of intrathymic islet allografts persisted for greater than 8 months after transplantation, and thymectomy (graft removal) did not precipitate hyperglycemia.

CONCLUSIONS: Prophylactic intrathymic MHC-incompatible islet allografts effectively prevent hyperglycemia and native beta-cell destruction in an animal model of autoimmune diabetes. Rejection and autoimmune destruction of intrathymic MHC-incompatible islet allografts were not seen after transplantation in the prediabetic (prehyperglycemic) period. Intrathymic islet allografts at an early age (before puberty) preserve native beta-cell function and may prevent or retard thymic atrophy.