Abstract
An examination of thymocytes and peripheral T cells from SHP-1-deficient motheaten mice possessing a transgenic MHC class I-restricted TCR has implicated SHP-1 in regulating TCR signaling thresholds at three checkpoints in T cell development and activation. First, in the population of CD4-CD8- double negative thymocytes, SHP-1 appears capable of regulating signals from TCR complexes that control the maturation and proliferation of double negative thymocytes. Second, the loss of SHP-1 increased the number of CD4+CD8+ double positive thymocytes capable of maturing as TCRhigh single positive thymocytes. Third, the loss of SHP-1 altered the basal level of activation of naive lymph node T cells. Accordingly, SHP-1-deficient lymph node T cells bearing the transgenic TCR demonstrated a hyperresponsiveness to stimulation with cognate peptide. However, the loss of SHP-1 did not alter the cytolytic ability of mature effector cytotoxic T lymphocytes. Together these results suggest that SHP-1 contributes to establishing thresholds for TCR signaling in thymocytes and naive peripheral T cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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CD3 Complex / metabolism
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CD4-CD8 Ratio
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Cell Differentiation / genetics
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Cell Differentiation / immunology
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Cytotoxicity, Immunologic
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Histocompatibility Antigens Class I / immunology
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Interleukin-2 / metabolism
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Intracellular Signaling Peptides and Proteins
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Lymph Nodes / immunology
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Lymph Nodes / pathology
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Lymphocyte Activation* / genetics
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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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Phosphotyrosine / metabolism
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Protein Tyrosine Phosphatase, Non-Receptor Type 11
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Protein Tyrosine Phosphatase, Non-Receptor Type 6
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Protein Tyrosine Phosphatases / deficiency
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Protein Tyrosine Phosphatases / genetics
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Protein Tyrosine Phosphatases / physiology*
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Receptors, Antigen, T-Cell / genetics
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Receptors, Antigen, T-Cell / immunology
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Receptors, Antigen, T-Cell / physiology*
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Signal Transduction / genetics
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Signal Transduction / immunology*
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T-Lymphocytes / cytology
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T-Lymphocytes / enzymology*
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T-Lymphocytes / immunology*
Substances
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CD3 Complex
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Histocompatibility Antigens Class I
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Interleukin-2
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Intracellular Signaling Peptides and Proteins
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Receptors, Antigen, T-Cell
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Phosphotyrosine
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Protein Tyrosine Phosphatase, Non-Receptor Type 11
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Protein Tyrosine Phosphatase, Non-Receptor Type 6
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Protein Tyrosine Phosphatases
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Ptpn11 protein, mouse
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Ptpn6 protein, mouse