Sites of the Defects Leading to Autoimmunity in the Spontaneously Diabetic BB Rat
Although spontaneous hyperglycemic syndromes have long been recognized in a variety of species, only a very few appear to have an autoimmune pathogenesis. To date, the animal model most closely resembling human Type I diabetes mellitus is the BB rat (1,2, for reviews). The BB rat syndrome is characterized by a sudden onset of severe hyperglycemia associated with ketoacidosis, weight loss, and virtually complete pancreatic beta cell depletion, followed by death within a few days unless insulin is administered. Onset of hyperglycemia occurs in approximately 70 percent of diabetes-prone littermates, usually between 60 and 120 days of age. As in humans, susceptibility to diabetes is associated with the major histocompatibility complex (MHC). The BB rat also exhibits profound T-lymphocytopenia, antedating onset of diabetes and demonstrating a marked decrease in both T-helper/inducer (Th/Ti) and T-cytotoxic/suppressor (TcTs) cell populations. As is typical of autoimmunity in other animals, BB rat l3rniphocytes show depressed responsiveness to concanavalin A (ConA) and to allogeneic stimulator cells in mixed lymphocyte reactions (MLRs). The autoimmune nature of the syndrome in BB rats is evidenced by the presence of an intense mononuclear infiltration of the pancreatic islets (insulitis) and the presence in serum of various autoantibodies, including antibodies directed against surface determinants of islet cells (1,2, for reviews).
KeywordsBone Marrow Stem Cell Bone Marrow Chimera Bone Marrow Recipient Neonatal Thymectomy Thymus Graft
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