Abstract
Immune defense against pathogens often requires NO, synthesized by type 2 NO synthase (NOS2). To discern whether this axis could participate in an autoimmune response, we immunized NOS2-deficient mice with the autoantigen acetylcholine receptor, inducing muscle weakness characteristic of myasthenia gravis, a T cell-dependent Ab-mediated autoimmune disease. We found that the acetylcholine receptor-immunized NOS2-deficient mice developed an exacerbated form of myasthenia gravis, and demonstrated that NOS2 expression limits autoreactive T cell determinant spreading and diversification of the autoantibody repertoire, a process driven by macrophages. Thus, NOS2/NO is important for silencing autoreactive T cells and may restrict bystander autoimmune reactions following the innate immune response.
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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Amino Acid Sequence
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Animals
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Autoantibodies / blood
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Autoantigens / administration & dosage
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Autoimmunity / physiology*
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Immunization
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Interferon-gamma / biosynthesis
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Interleukin-4 / biosynthesis
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Mice
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Mice, Knockout
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Molecular Sequence Data
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Myasthenia Gravis, Autoimmune, Experimental / etiology
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Myasthenia Gravis, Autoimmune, Experimental / immunology
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Nitric Oxide / biosynthesis
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Nitric Oxide Synthase / deficiency
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Nitric Oxide Synthase / genetics
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Nitric Oxide Synthase / immunology*
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Nitric Oxide Synthase Type II
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Peptide Fragments / chemistry
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Peptide Fragments / genetics
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Peptide Fragments / immunology
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Receptors, Cholinergic / chemistry
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Receptors, Cholinergic / genetics
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Receptors, Cholinergic / immunology
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T-Lymphocytes / immunology
Substances
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Autoantibodies
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Autoantigens
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Peptide Fragments
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Receptors, Cholinergic
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Interleukin-4
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Nitric Oxide
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Interferon-gamma
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Nitric Oxide Synthase
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Nitric Oxide Synthase Type II
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Nos2 protein, mouse