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© 2001 by the American Diabetes Association, Inc.
Development and Function of Diabetogenic T-cells in B-cell–Deficient Nonobese Diabetic Mice
1 Program in Developmental Biology, the Hospital for Sick Children Research Institute
2 Departments of Surgery and
3 Immunology and the
4 Institute of Medical Science, University of Toronto, Ontario, Canada
5 Jackson Laboratory, Bar Harbor, Maine
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.µMT) 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.µMT 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.
Abbreviations: Ab, antibody; Ag, antigen; APC, Ag-presenting cell; BSA, bovine serum albumin; Cµ2A, Ig Cµ; 3'-primer; DC; dendritic cell; FACS, fluorescence-activated cell sorter; FITC, fluorescein isothiocyanate; FT, fetal thymus; Igh, Ig heavy chain; KLH, keyhole limpet hemocyanin; LN, lymph node; mAb, monoclonal antibody; MHC, major histocompatibility complex; µMT, Igµ constant transmembrane region; PBL, peripheral blood lymphocyte; PBS, phosphate-buffered saline; PI, propidium iodide; RT-PCR, reverse transcriptase–polymerase chain reaction; VHALL, Ig Vh 5'-primer
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