Abstract
CD25(+)CD4(+) regulatory T cells in normal animals are engaged in the maintenance of immunological self-tolerance. We show here that glucocorticoid-induced tumor necrosis factor receptor family-related gene (GITR, also known as TNFRSF18)--a member of the tumor necrosis factor-nerve growth factor (TNF-NGF) receptor gene superfamily--is predominantly expressed on CD25(+)CD4(+) T cells and on CD25(+)CD4(+)CD8(-) thymocytes in normal naïve mice. We found that stimulation of GITR abrogated CD25(+)CD4(+) T cell-mediated suppression. In addition, removal of GITR-expressing T cells or administration of a monoclonal antibody to GITR produced organ-specific autoimmune disease in otherwise normal mice. Thus, GITR plays a key role in dominant immunological self-tolerance maintained by CD25(+)CD4(+) regulatory T cells and could be a suitable molecular target for preventing or treating autoimmune disease.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Autoimmune Diseases / etiology
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CD4 Antigens / isolation & purification
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CD4-Positive T-Lymphocytes / immunology*
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Dimerization
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Glucocorticoid-Induced TNFR-Related Protein
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Glycoproteins / antagonists & inhibitors
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Glycoproteins / immunology
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Glycoproteins / metabolism
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Immune Tolerance / immunology*
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Lymph Nodes / immunology
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Mice
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Mice, Inbred BALB C
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Rats
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Rats, Wistar
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Receptors, Interleukin-2 / isolation & purification
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Receptors, Nerve Growth Factor / antagonists & inhibitors
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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 / antagonists & inhibitors
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Receptors, Tumor Necrosis Factor / immunology
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Receptors, Tumor Necrosis Factor / metabolism*
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Signal Transduction
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Spleen / immunology
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T-Lymphocyte Subsets / immunology*
Substances
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CD4 Antigens
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Glucocorticoid-Induced TNFR-Related Protein
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Glycoproteins
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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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Tnfrsf18 protein, mouse