Abstract
THE BIOBREEDING (BB) rat strain is used to model human autoimmune insulin-dependent diabetes mellitus (IDDM). 1 The diabetes-resistant (DR) subline of the BB rat does not develop diabetes spontaneously, but is genetically predisposed to the disorder. 1 More than 90% of BB-DR rats become diabetic after combined treatment with a depleting monoclonal antibody (MAb) to remove RT6.1 + regulatory T cells and polyinosinic:polycytidylic acid (poly I:C), an inducer of interferons. 2 Lymph node T cells from diabetic BB-DR rats adoptively transfer IDDM to untreated histocompatible (RTI u) WAG- nu/nu rats. 3,4 Thymocytes from either normal or diabetic BB-DR rats also transfer IDDM provided that recipients are treated with anti-RT6.1 MAb to preclude maturation of RT6 + regulatory T cells from the transfused thymocytes. 5 We have previously observed that other rat strains that express the RT6.1 alloantigen, among them the YO (RTI u) and LEW (RT1 1) strains do not develop autoimmune diabetes when treated in the same way as BB-DR rats. 6 To investigate further if combination treatment with anti-RT6.1 MAb and poly I:C can induce autoimmunity in strains other than the BB, we studied major histocompatibility complex (MHC) congenic PVG.RTI u rats. These animals are phenotypically normal and free of spontaneous disease but reportedly develop IDDM after irradiation and thymectomy. 7
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