Abstract
The T cell receptor (TCR) requirements in the pathogenesis of insulin-dependent diabetes were examined with transgenic NOD mice bearing nondisease-related TCR alpha and beta chains. In both TCR beta and TCR alpha beta transgenic NOD mice the beta chain transgene was expressed by > 98% of peripheral T cells. The alpha chain transgene was also highly expressed. Insulitis developed in both sets of transgenic animals with most of the lymphocytes in the lesion expressing the transgenic beta chain and with depletion of the endogenous TCR V beta genes. Nonetheless, NOD animals transgenic for TCR beta and TCR alpha beta developed diabetes similar to controls. Thus, skewing the TCR repertoire did not diminish autoimmune susceptibility in NOD mice.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Aging / physiology
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Animals
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Base Sequence
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Crosses, Genetic
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Diabetes Mellitus, Type 2 / genetics
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Diabetes Mellitus, Type 2 / immunology
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Diabetes Mellitus, Type 2 / physiopathology*
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Female
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Gene Rearrangement, T-Lymphocyte
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Islets of Langerhans / immunology
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Islets of Langerhans / pathology
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Male
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Mice
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Mice, Inbred NOD / physiology*
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Mice, Transgenic
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Molecular Sequence Data
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Oligodeoxyribonucleotides
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Pancreatic Diseases / genetics
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Pancreatic Diseases / immunology
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Pancreatic Diseases / pathology
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Polymerase Chain Reaction / methods
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Receptors, Antigen, T-Cell, alpha-beta / genetics
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Receptors, Antigen, T-Cell, alpha-beta / physiology*
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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, alpha-beta