Abstract
Targeted immune regulation can be achieved by use of tissue-specific T cells and offers the potential for organ-specific suppression of destructive autoimmune processes. Here, we report the generation and characterization of insulin B chain-specific "autoreactive" CD4+ regulatory T cells that locally suppress diabetogenic T cell responses against an unrelated self-antigen (viral transgene) in a virus-induced model for type 1 diabetes. Interleukin 4 (IL-4) is essential for prevention of diabetes since regulatory T cells cannot be induced in the absence of IL-4 or stat6 (IL-4 signaling pathway). Our observations demonstrate that autoreactive regulatory T cells can suppress autoreactive destructive T cell activity of differential antigenic specificity locally in the pancreatic draining lymph node, probably via cytokine-mediated modulation of antigen-presenting cells.
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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Administration, Oral
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Adoptive Transfer*
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Animals
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Autoimmune Diseases / immunology
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Autoimmune Diseases / prevention & control*
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Autoimmune Diseases / virology
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Autoimmunity*
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CD4-Positive T-Lymphocytes / immunology*
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Diabetes Mellitus, Type 1 / immunology
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Diabetes Mellitus, Type 1 / prevention & control*
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Diabetes Mellitus, Type 1 / virology
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Insulin / immunology*
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Interferon-gamma / physiology
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Interleukin-10 / physiology
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Interleukin-4 / physiology*
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Lymph Nodes / immunology
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Lymphocytic Choriomeningitis / immunology
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Lymphocytic choriomeningitis virus / genetics
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Lymphocytic choriomeningitis virus / immunology
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Mice
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Mice, Inbred BALB C
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Mice, Transgenic
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Nucleoproteins / genetics
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Nucleoproteins / immunology
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Pancreas / immunology
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Peptide Fragments / immunology*
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Promoter Regions, Genetic
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Recombinant Fusion Proteins / immunology
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STAT6 Transcription Factor
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Swine
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T-Lymphocyte Subsets / immunology*
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Trans-Activators / physiology*
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Viral Proteins / genetics
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Viral Proteins / immunology
Substances
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Insulin
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Nucleoproteins
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Peptide Fragments
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Recombinant Fusion Proteins
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STAT6 Transcription Factor
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Stat6 protein, mouse
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Trans-Activators
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Viral Proteins
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Interleukin-10
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Interleukin-4
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Interferon-gamma