Abstract
The role of TCR signals triggered by recognition of self MHCs in maintaining the survival of naive peripheral T cells remains controversial. Here we examine the role of the Src family kinases, p56(lck) (Lck) and p59(fyn) (Fyn), in the survival of naive T cells. We show that long term survival requires a combination of signals transduced by Src family kinases and signals through the IL-7R. In the absence of either one, naive T cells die slowly, but if both signals are removed, cell loss is greatly accelerated. The TCR signal can be mediated by either Fyn or Lck at wild-type levels of expression, but not by Lck alone if expressed suboptimally. The disappearance of T cells in the absence of Fyn and Lck was associated with a complete loss of TCRzeta-chain phosphorylation and down-regulation of CD5, both of which are also MHC contact dependent, indicating that the Src family kinases are critical for transducing a TCR-MHC survival signal.
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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CD5 Antigens / biosynthesis
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Cell Survival / genetics
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Cell Survival / immunology
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Drug Synergism
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Gene Expression Regulation, Enzymologic / immunology
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Interphase / genetics
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Interphase / immunology
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Lymphocyte Count
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Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / biosynthesis
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Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / deficiency
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Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / genetics
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Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / physiology
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Lymphopenia / genetics
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Lymphopenia / immunology
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Phosphorylation
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Proto-Oncogene Proteins / deficiency
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / physiology
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Proto-Oncogene Proteins c-fyn
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Receptors, Antigen, T-Cell / metabolism
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Receptors, Antigen, T-Cell / physiology*
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Receptors, Interleukin-7 / physiology
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Signal Transduction / genetics
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Signal Transduction / immunology*
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T-Lymphocyte Subsets / cytology*
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T-Lymphocyte Subsets / enzymology*
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T-Lymphocyte Subsets / immunology
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T-Lymphocyte Subsets / metabolism
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Thymus Gland / cytology
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Thymus Gland / enzymology
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Thymus Gland / growth & development
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Transgenes / immunology
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src-Family Kinases / deficiency
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src-Family Kinases / genetics
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src-Family Kinases / physiology*
Substances
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CD3 Complex
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CD3 antigen, zeta chain
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CD5 Antigens
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Proto-Oncogene Proteins
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Receptors, Antigen, T-Cell
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Receptors, Interleukin-7
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Fyn protein, mouse
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Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
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Proto-Oncogene Proteins c-fyn
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src-Family Kinases