Susceptibility to diabetes is widely distributed in normal class IIu haplotype rats.

Aims/hypothesis: We did experiments to explore the pathways putatively leading to Type I (insulin-dependent) diabetes mellitus, and their association with the MHC locus, the major genetic determinant of disease susceptibility.

Methods: Normal MHC congenic rat strains that do not spontaneously develop diabetes or any other autoimmune syndrome were injected with the interferon-alpha inducer polyinosinic-polycytidylic acid (Poly IC).

Results: Insulitis and diabetes developed only in strains expressing Class II(u) genes and was independent of the Class I haplotype.

Islet cell membrane antigens activate diabetogenic CD4+ T-cells in the BB/Wor rat.

Type 1 diabetes is a major histocompatibility complex (MHC) class II-associated autoimmune disease mediated by beta-cell-specific T-cells and characterized by circulating autoantibodies to beta-cell molecules. In the BB/Wor diabetes-prone (DP) rat, type 1 diabetes develops spontaneously with an incidence of >90%. BB diabetes can be adoptively transferred to naive syngeneic or MHC class II-compatible rats with islet cell-activated T-cell lines derived from diabetic BB/Wor rats.

Kilham rat triggers T-cell-dependent autoimmune diabetes in multiple strains of rat.

Kilham rat virus (KRV) infection of BB/Wor diabetes-resistant (DR) RT1(u) rats induces autoimmune diabetes without direct cytolytic infection of pancreatic beta-cells and is a new model of virus-induced IDDM. To investigate genetic susceptibility to KRV-induced diabetes, major histocompatibility complex congenic and other inbred rats were infected with the virus and studied for the appearance of diabetes and insulitis. KRV infection alone induced insulitis, selective beta-cell necrosis, and diabetes in BB/Wor DR and LEW1.

Genetics of the BB rat: association of autoimmune disorders (diabetes, insulitis, and thyroiditis) with lymphopenia and major histocompatibility complex class II.

The BB/Wor rat develops spontaneous autoimmune diabetes mellitus and also frequently develops lymphocytic thyroiditis. To clarify the role of T cell lymphopenia and the major histocompatibility complex (MHC) in the development of these autoimmune disorders, we studied back-cross animals between the inbred thyroiditis and diabetes-prone BBNB/Wor subline (MHC RT1.AuBuDuCu) and three nonlymphopenic MHC-congenic rat strains: PVG.