Abstract
The mechanism by which antagonist peptides inhibit T cell responses is unknown. Mice deficient in Src homology 2 domain-containing protein tyrosine phosphatase (SHP-1) have revealed its importance in the negative regulation of lymphocyte signaling. We investigated a possible role for SHP-1 in T cell antagonism and demonstrate, for the first time, a substantial increase in SHP-1 activity during antagonism of CD4(+) T cells. Furthermore, the removal of functional SHP-1 prevents antagonism in these cells. Our data demonstrate that T cell antagonism occurs via a negative intracellular signal that is mediated by SHP-1.
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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CD4-Positive T-Lymphocytes / enzymology
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / metabolism
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Catalytic Domain / genetics
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Catalytic Domain / immunology
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Cells, Cultured
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Down-Regulation / genetics
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Down-Regulation / immunology*
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Enzyme Activation / genetics
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Enzyme Activation / immunology
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Gene Deletion
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Genetic Vectors
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Humans
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Immunophenotyping
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Intracellular Signaling Peptides and Proteins
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Lymphocyte Activation / genetics
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Lymphocyte Activation / immunology
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Mice
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Mice, Inbred A
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Mice, Inbred C57BL
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Mice, Transgenic
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Phosphorylation
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Protein Tyrosine Phosphatase, Non-Receptor Type 6
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Protein Tyrosine Phosphatases / antagonists & inhibitors
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Protein Tyrosine Phosphatases / genetics
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Protein Tyrosine Phosphatases / metabolism*
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Protein Tyrosine Phosphatases / physiology
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Receptors, Antigen, T-Cell / antagonists & inhibitors*
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Receptors, Antigen, T-Cell / immunology
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Receptors, Antigen, T-Cell / metabolism
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Signal Transduction / genetics
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Signal Transduction / immunology
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src Homology Domains / immunology*
Substances
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Intracellular Signaling Peptides and Proteins
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Receptors, Antigen, T-Cell
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PTPN6 protein, human
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Protein Tyrosine Phosphatase, Non-Receptor Type 6
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Protein Tyrosine Phosphatases
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Ptpn6 protein, mouse