Abstract
Experimental autoimmune thyroiditis (EAT), a model for Hashimoto's thyroiditis, is a T cell-mediated disease inducible with mouse thyroglobulin (mTg). Pretreatment with mTg, however, can induce CD4+ T cell-mediated tolerance to EAT. We demonstrate that CD4+CD25+ regulatory cells are critical for the tolerance induction, as in vivo depletion of CD25+ cells abrogated established tolerance, and CD4+CD25+ cells from tolerized mice suppressed mTg-responsive cells in vitro. Importantly, administration of an agonistic CD137 monoclonal antibody (mAb) inhibited tolerance development, and the mediation of established tolerance. CD137 mAb also inhibited the suppression of mTg-responsive cells by CD4+CD25+ cells in vitro. Signaling through CD137 likely resulted in enhancement of the responding inflammatory T cells, as anti-CD137 did not enable CD4+CD25+ T cells to proliferate in response to mTg in vitro.
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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Animals
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Antibodies, Monoclonal / administration & dosage
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Antibodies, Monoclonal / immunology
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Antigens, CD
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CD4-Positive T-Lymphocytes / immunology*
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CD4-Positive T-Lymphocytes / metabolism
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Female
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Immune Tolerance / physiology*
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Lymphocyte Activation*
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Mice
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Mice, Inbred CBA
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Receptors, Interleukin-2 / immunology*
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Receptors, Nerve Growth Factor / immunology
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Receptors, Nerve Growth Factor / metabolism*
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Receptors, Tumor Necrosis Factor / immunology
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Receptors, Tumor Necrosis Factor / metabolism*
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Signal Transduction / physiology*
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Thyroglobulin / immunology
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Thyroiditis, Autoimmune / metabolism*
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Tumor Necrosis Factor Receptor Superfamily, Member 9
Substances
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Antibodies, Monoclonal
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Antigens, CD
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Receptors, Interleukin-2
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Receptors, Nerve Growth Factor
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Receptors, Tumor Necrosis Factor
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Tnfrsf9 protein, mouse
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Tumor Necrosis Factor Receptor Superfamily, Member 9
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Thyroglobulin