title: Development and function of diabetogenic T-cells in B-cell-deficient nonobese diabetic mice.
abstract: Insulin-dependent diabetes (type 1 diabetes) in the NOD mouse is a T-cell-mediated autoimmune disease. However, B-cells may also play a critical role in disease pathogenesis, as genetically B-cell-deficient NOD mice (NOD.microMT) have been shown to be protected from type 1 diabetes and to display reduced responses to certain islet autoantigens. To examine the requirements for B-cells in the development of type 1 diabetes, we generated a B-cell-naive T-cell repertoire by transplantation of NOD fetal thymuses (FTs) into NOD.scid recipients. Surprisingly, these FT-derived NOD T-cells were diabetogenic in 36% of NOD.scid recipients, despite the absence of B-cells. In addition, T-cells isolated from NOD.microMT mice were diabetogenic in 22% of NOD.scid recipients. Together, these results indicate that B-cells are not an absolute requirement for the generation or effector function of an islet-reactive T-cell repertoire in NOD mice. We suggest that conditions favoring rapid lymphocyte expansion can reveal autoreactive T-cell activity and precipitate disease in genetically susceptible individuals.
authors: Hospital for Sick Children Research Institute,  Department of Surgery, University of Toronto, Ontario, Canada.
authors: P P
authors: PP
authors: Chiu
authors: D V
authors: DV
authors: Serreze
authors: J S
authors: JS
authors: Danska
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000473:pathology / Q000502:physiology*; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology*; D005260:Female; D016332:Fetal Tissue Transplantation; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD / Q000033:anatomy & histology* / Q000502:physiology*; D016513:Mice, SCID; D010179:Pancreas / Q000473:pathology; D013601:T-Lymphocytes / Q000502:physiology*