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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
1999-10-4
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pubmed:abstractText |
The selection events shaping T cell development in the thymus represent the outcome of TCR-driven intracellular signaling cascades evoked by Ag receptor interaction with cognate ligand. In view of data indicating TCR-evoked thymocyte proliferation to be negatively modulated by the SHP-1 tyrosine phosphatase, a potential role for SHP-1 in regulating selection processes was investigated by analysis of T cell development in H-Y TCR transgenic mice rendered SHP-1 deficient by introduction of the viable motheaten mutation or a dominant negative SHP-1-encoding transgene. Characterization of thymocyte and peripheral T cell populations in H-Y TCR-viable motheaten mice revealed TCR-evoked proliferation as well as the positive and negative selection of H-Y-specific thymocytes to be enhanced in these mice, thus implicating SHP-1 in the negative regulation of each of these processes. T cell selection processes were also augmented in H-Y TCR mice carrying a transgene driving lymphoid-restricted expression of a catalytically inert, dominant-negative form of SHP-1. SHP-1-negative effects on thymocyte TCR signaling were not influenced by co-cross-linking of the CD28 costimulatory and/or CTLA-4 inhibitory receptors and appear, accordingly, to be realized independently of these comodulators. These observations indicate that SHP-1 raises the signaling threshold required for both positive and negative selection and reveal the inhibitory effects of SHP-1 on TCR signaling to be cell autonomous. The demonstrated capacity for SHP-1 to inhibit TCR-evoked proliferation and selection indicate SHP-1 modulatory effects on the magnitude of TCR-generated signal to be a key factor in determining the cellular consequences of TCR-ligand interaction.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD28,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD3,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Differentiation,
http://linkedlifedata.com/resource/pubmed/chemical/CTLA-4 Antigen,
http://linkedlifedata.com/resource/pubmed/chemical/Ctla4 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/H-Y Antigen,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoconjugates,
http://linkedlifedata.com/resource/pubmed/chemical/Immunosuppressive Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Tyrosine Phosphatase...,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Tyrosine Phosphatase...,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Tyrosine Phosphatases,
http://linkedlifedata.com/resource/pubmed/chemical/Ptpn11 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Ptpn6 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Antigen, T-Cell,
http://linkedlifedata.com/resource/pubmed/chemical/SH2 Domain-Containing Protein...,
http://linkedlifedata.com/resource/pubmed/chemical/abatacept
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0022-1767
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
163
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3012-21
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:10477564-Animals,
pubmed-meshheading:10477564-Antibodies, Monoclonal,
pubmed-meshheading:10477564-Antigens, CD,
pubmed-meshheading:10477564-Antigens, CD28,
pubmed-meshheading:10477564-Antigens, CD3,
pubmed-meshheading:10477564-Antigens, Differentiation,
pubmed-meshheading:10477564-CTLA-4 Antigen,
pubmed-meshheading:10477564-Cell Differentiation,
pubmed-meshheading:10477564-Female,
pubmed-meshheading:10477564-Gene Expression Regulation,
pubmed-meshheading:10477564-H-Y Antigen,
pubmed-meshheading:10477564-Immunoconjugates,
pubmed-meshheading:10477564-Immunosuppressive Agents,
pubmed-meshheading:10477564-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:10477564-Lymphocyte Activation,
pubmed-meshheading:10477564-Male,
pubmed-meshheading:10477564-Mice,
pubmed-meshheading:10477564-Mice, Inbred C57BL,
pubmed-meshheading:10477564-Mice, Mutant Strains,
pubmed-meshheading:10477564-Mice, Transgenic,
pubmed-meshheading:10477564-Protein Tyrosine Phosphatase, Non-Receptor Type 11,
pubmed-meshheading:10477564-Protein Tyrosine Phosphatase, Non-Receptor Type 6,
pubmed-meshheading:10477564-Protein Tyrosine Phosphatases,
pubmed-meshheading:10477564-Receptors, Antigen, T-Cell,
pubmed-meshheading:10477564-SH2 Domain-Containing Protein Tyrosine Phosphatases,
pubmed-meshheading:10477564-Signal Transduction,
pubmed-meshheading:10477564-T-Lymphocyte Subsets,
pubmed-meshheading:10477564-Transgenes,
pubmed-meshheading:10477564-src Homology Domains
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pubmed:year |
1999
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pubmed:articleTitle |
Involvement of the SHP-1 tyrosine phosphatase in regulation of T cell selection.
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pubmed:affiliation |
Department of Immunology, University of Toronto, The Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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