Abstract
Initiation of diabetes in NOD mice can be mediated by the costimulatory signals received by T cells. The ICOS is found on Ag-experienced T cells where it acts as a potent regulator of T cell responses. To determine the function of ICOS in diabetes, we followed the course of autoimmune disease and examined T cells in ICOS-deficient NOD mice. The presence of ICOS was indispensable for the development of insulitis and hyperglycemia in NOD mice. In T cells, the deletion of ICOS resulted in a decreased production of the Th1 cytokine IFN-gamma, whereas the numbers of regulatory T cells remained unchanged. We conclude that ICOS is critically important for the induction of the autoimmune process that leads to diabetes.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens, Differentiation, T-Lymphocyte / genetics
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Antigens, Differentiation, T-Lymphocyte / physiology*
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Autoantibodies / blood
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Diabetes Mellitus, Type 1 / immunology*
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Diabetes Mellitus, Type 1 / metabolism*
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Diabetes Mellitus, Type 1 / pathology
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Diabetes Mellitus, Type 1 / prevention & control
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Down-Regulation / genetics
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Down-Regulation / immunology
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Female
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Forkhead Transcription Factors / antagonists & inhibitors
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Inducible T-Cell Co-Stimulator Protein
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Interferon-gamma / antagonists & inhibitors
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Interferon-gamma / biosynthesis
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Interleukin-2 Receptor alpha Subunit / biosynthesis
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Islets of Langerhans / immunology
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Islets of Langerhans / pathology
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Lymphocyte Count
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Mice
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Mice, Inbred NOD
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Mice, Knockout
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T-Lymphocytes, Regulatory / immunology
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T-Lymphocytes, Regulatory / metabolism
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Th1 Cells / immunology
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Th1 Cells / metabolism
Substances
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Antigens, Differentiation, T-Lymphocyte
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Autoantibodies
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Forkhead Transcription Factors
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Foxp3 protein, mouse
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Icos protein, mouse
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Inducible T-Cell Co-Stimulator Protein
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Interleukin-2 Receptor alpha Subunit
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Interferon-gamma