Abstract
Nonobese diabetic (NOD) mice spontaneously develop a disease very similar to type 1 diabetes in humans. We have generated a transgenic mouse strain carrying the rearranged T cell receptor genes from a diabetogenic T cell clone derived from a NOD mouse. Self-reactive T cells expressing the transgene-encoded specificity are not tolerized in these animals, resulting in rampant insulitis and eventually diabetes. Features of the disease process emphasize two so-called check-points, recognized previously in the NOD and human diseases but easily misinterpreted. Although NOD mice are protected from insulitis and diabetes by expression of the E molecule encoded in the major histocompatibility complex, the transgenics are not, permitting us to exclude some possible mechanisms of protection.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Base Sequence
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Diabetes Mellitus, Type 1 / genetics*
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Diabetes Mellitus, Type 1 / immunology*
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Flow Cytometry
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Gene Rearrangement, T-Lymphocyte*
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Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor
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Gene Rearrangement, beta-Chain T-Cell Antigen Receptor
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Islets of Langerhans / immunology
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Islets of Langerhans / pathology
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Mice
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Mice, Inbred NOD / immunology
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Mice, Transgenic
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Molecular Sequence Data
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Oligodeoxyribonucleotides
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Pancreas / immunology
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Pancreas / pathology
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Polymerase Chain Reaction / methods
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Receptors, Antigen, T-Cell / biosynthesis
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Receptors, Antigen, T-Cell / genetics*
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Receptors, Antigen, T-Cell, alpha-beta / biosynthesis
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Receptors, Antigen, T-Cell, alpha-beta / genetics*
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Submandibular Gland / immunology
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Submandibular Gland / pathology
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T-Lymphocytes / immunology*
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T-Lymphocytes / pathology
Substances
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Oligodeoxyribonucleotides
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Receptors, Antigen, T-Cell
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Receptors, Antigen, T-Cell, alpha-beta