Abstract
PTEN, a tumor suppressor gene, is essential for embryogenesis. We used the Cre-loxP system to generate a T cell-specific deletion of the Pten gene (Pten(flox/-) mice). All Pten(flox/-) mice develop CD4+ T cell lymphomas by 17 weeks. Pten(flox/-) mice show increased thymic cellularity due in part to a defect in thymic negative selection. Pten(flox/-) mice exhibit elevated levels of B cells and CD4+ T cells in the periphery, spontaneous activation of CD4+ T cells, autoantibody production, and hypergammaglobulinemia. Pten(flox/-) T cells hyperproliferate, are autoreactive, secrete increased levels of Th1/Th2 cytokines, resist apoptosis, and show increased phosphorylation of PKB/Akt and ERK. Peripheral tolerance to SEB is also impaired in Pten(flox/-) mice. PTEN is thus an important regulator of T cell homeostasis and self-tolerance.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis / immunology
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CD4-Positive T-Lymphocytes / cytology
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CD4-Positive T-Lymphocytes / immunology*
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Cell Division
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Cytokines / biosynthesis
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DNA-Binding Proteins / metabolism
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Enterotoxins / immunology
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Female
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Genes, Tumor Suppressor*
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I-kappa B Proteins*
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Immune Tolerance*
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Lymphatic Diseases / immunology
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Lymphoma, T-Cell / immunology
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Mice, Transgenic
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Mitogen-Activated Protein Kinases / metabolism
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PTEN Phosphohydrolase
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Phosphoric Monoester Hydrolases / genetics
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Phosphoric Monoester Hydrolases / immunology*
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Protein Serine-Threonine Kinases*
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-akt
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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Receptors, Antigen / genetics
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Receptors, Antigen / immunology
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Receptors, Antigen, T-Cell / genetics
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Receptors, Antigen, T-Cell / immunology
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Splenomegaly
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Staphylococcus aureus / immunology
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Superantigens / immunology
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Thymus Gland / abnormalities
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Thymus Gland / cytology
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Tumor Suppressor Proteins*
Substances
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Cytokines
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DNA-Binding Proteins
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Enterotoxins
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H-Y antigen receptor
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I kappa B beta protein
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I-kappa B Proteins
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-2
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Receptors, Antigen
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Receptors, Antigen, T-Cell
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Superantigens
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Tumor Suppressor Proteins
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enterotoxin B, staphylococcal
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-akt
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Mitogen-Activated Protein Kinases
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Phosphoric Monoester Hydrolases
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PTEN Phosphohydrolase