Abstract
Protein tyrosine kinases and phosphatases cooperate to regulate normal immune cell function. We examined the role of PEST domain-enriched tyrosine phosphatase (PEP) in regulating T cell antigen-receptor function during thymocyte development and peripheral T cell differentiation. Although normal naïve T cell functions were retained in pep-deficient mice, effector/memory T cells demonstrated enhanced activation of Lck. In turn, this resulted in increased expansion and function of the effector/memory T cell pool, which was also associated with spontaneous development of germinal centers and elevated serum antibody levels. These results revealed a central role for PEP in negatively regulating specific aspects of T cell development and function.
MeSH terms
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Animals
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Autoimmunity
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B-Lymphocytes / physiology
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / physiology
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CD8-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / physiology
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Cell Cycle
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Gene Targeting
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Germinal Center / physiology
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Hydrogen-Ion Concentration
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Immunoglobulins / blood
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Immunologic Memory*
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Lymphocyte Activation
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Lymphocyte Count
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Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / metabolism
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Mice
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Mice, Inbred BALB C
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Mice, Transgenic
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Phosphorylation
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Protein Tyrosine Phosphatase, Non-Receptor Type 12
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Protein Tyrosine Phosphatases / genetics
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Protein Tyrosine Phosphatases / metabolism*
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Receptors, Antigen, T-Cell / genetics
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Receptors, Antigen, T-Cell / immunology
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Signal Transduction
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T-Lymphocyte Subsets / immunology
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T-Lymphocytes / immunology*
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T-Lymphocytes / physiology
Substances
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Immunoglobulins
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Receptors, Antigen, T-Cell
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Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
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Protein Tyrosine Phosphatase, Non-Receptor Type 12
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Protein Tyrosine Phosphatases
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Ptpn12 protein, mouse