Abstract
The dynamics of CD4(+) effector T cells (Teff cells) and CD4(+)Foxp3(+) regulatory T cells (Treg cells) during diabetes progression in nonobese diabetic mice was investigated to determine whether an imbalance of Treg cells and Teff cells contributes to the development of type 1 diabetes. Our results demonstrated a progressive decrease in the Treg cell:Teff cell ratio in inflamed islets but not in pancreatic lymph nodes. Intra-islet Treg cells expressed reduced amounts of CD25 and Bcl-2, suggesting that their decline was due to increased apoptosis. Additionally, administration of low-dose interleukin-2 (IL-2) promoted Treg cell survival and protected mice from developing diabetes. Together, these results suggest intra-islet Treg cell dysfunction secondary to defective IL-2 production is a root cause of the progressive breakdown of self-tolerance and the development of diabetes in nonobese diabetic mice.
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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Autoimmunity*
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CD4-Positive T-Lymphocytes / cytology
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / metabolism*
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Cell Survival
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Diabetes Mellitus, Type 1 / immunology
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Diabetes Mellitus, Type 1 / metabolism*
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Interleukin-2 / immunology
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Interleukin-2 / metabolism*
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Interleukin-2 Receptor alpha Subunit / immunology
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Interleukin-2 Receptor alpha Subunit / metabolism
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Islets of Langerhans / immunology*
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Lymph Nodes / cytology
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Lymph Nodes / immunology
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Lymph Nodes / metabolism
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Lymphocyte Activation
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Mice
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Mice, Inbred NOD
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Proto-Oncogene Proteins c-bcl-2 / immunology
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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T-Lymphocytes, Regulatory / cytology
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T-Lymphocytes, Regulatory / immunology*
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T-Lymphocytes, Regulatory / metabolism
Substances
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Interleukin-2
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Interleukin-2 Receptor alpha Subunit
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Proto-Oncogene Proteins c-bcl-2