Abstract
The phenotype of NFATc2(-/-) c3(-/-) (double knockout [DKO]) mice implies a disturbed regulation of T cell responses, evidenced by massive lymphadenopathy, splenomegaly, and autoaggressive phenomena. The population of CD4(+) CD25(+) T cells from DKO mice lacks regulatory capacity, except a small subpopulation that highly expresses glucocorticoid-induced tumor necrosis factor receptor family-related gene (GITR) and CD25. However, neither wild-type nor DKO CD4(+) CD25(+) regulatory T cells (T reg cells) are able to suppress proliferation of DKO CD4(+) CD25(-) T helper cells. Therefore, combined NFATc2/c3 deficiency is compatible with the development of CD4(+) CD25(+) T reg cells but renders conventional CD4(+) T cells unresponsive to suppression, underlining the importance of NFAT proteins for sustaining T cell homeostasis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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CD4-Positive T-Lymphocytes / metabolism*
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Coculture Techniques
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DNA-Binding Proteins / deficiency
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Glucocorticoid-Induced TNFR-Related Protein
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Lymphocyte Activation
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Mice
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Mice, Knockout
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NFATC Transcription Factors
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Nuclear Proteins / deficiency
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism*
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Receptors, Interleukin-2 / deficiency
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Receptors, Interleukin-2 / genetics
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Receptors, Interleukin-2 / metabolism*
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Receptors, Nerve Growth Factor / metabolism
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Receptors, Tumor Necrosis Factor / metabolism
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T-Lymphocyte Subsets / metabolism*
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Transcription Factors / deficiency
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Transcription Factors / genetics
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Transcription Factors / metabolism*
Substances
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DNA-Binding Proteins
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Glucocorticoid-Induced TNFR-Related Protein
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NFATC Transcription Factors
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Nfatc2 protein, mouse
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Nfatc3 protein, mouse
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Nuclear Proteins
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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
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Transcription Factors