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rdf:type |
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lifeskim:mentions |
umls-concept:C0025260,
umls-concept:C0034790,
umls-concept:C0039194,
umls-concept:C0079411,
umls-concept:C0085358,
umls-concept:C0546816,
umls-concept:C1332717,
umls-concept:C1413244,
umls-concept:C1517945,
umls-concept:C1706438,
umls-concept:C1710082,
umls-concept:C2698600
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pubmed:issue |
25
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pubmed:dateCreated |
2010-12-17
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pubmed:abstractText |
The requirements for tonic T-cell receptor (TCR) signaling in CD8(+) memory T-cell generation and homeostasis are poorly defined. The SRC homology 2 (SH2)-domain-containing leukocyte protein of 76 kDa (SLP-76) is critical for proximal TCR-generated signaling. We used temporally mediated deletion of SLP-76 to interrupt tonic and activating TCR signals after clearance of the lymphocytic choriomeningitis virus (LCMV). SLP-76-dependent signals are required during the contraction phase of the immune response for the normal generation of CD8 memory precursor cells. Conversely, LCMV-specific memory CD8 T cells generated in the presence of SLP-76 and then acutely deprived of TCR-mediated signals persist in vivo in normal numbers for more than 40 weeks. Tonic TCR signals are not required for the transition of the memory pool toward a central memory phenotype, but the absence of SLP-76 during memory homeostasis substantially alters the kinetics. Our data are consistent with a model in which tonic TCR signals are required at multiple stages of differentiation, but are dispensable for memory CD8 T-cell persistence.
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pubmed:grant |
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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 |
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
1528-0020
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
16
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pubmed:volume |
116
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
5560-70
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pubmed:dateRevised |
2011-9-26
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pubmed:meshHeading |
pubmed-meshheading:20884806-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:20884806-Animals,
pubmed-meshheading:20884806-Blotting, Western,
pubmed-meshheading:20884806-CD8-Positive T-Lymphocytes,
pubmed-meshheading:20884806-Cell Differentiation,
pubmed-meshheading:20884806-Cell Proliferation,
pubmed-meshheading:20884806-Female,
pubmed-meshheading:20884806-Flow Cytometry,
pubmed-meshheading:20884806-Immunologic Memory,
pubmed-meshheading:20884806-Lymphocyte Activation,
pubmed-meshheading:20884806-Lymphocytic Choriomeningitis,
pubmed-meshheading:20884806-Lymphocytic choriomeningitis virus,
pubmed-meshheading:20884806-Male,
pubmed-meshheading:20884806-Mice,
pubmed-meshheading:20884806-Mice, Inbred C57BL,
pubmed-meshheading:20884806-Mice, Knockout,
pubmed-meshheading:20884806-Mice, Transgenic,
pubmed-meshheading:20884806-Phosphoproteins,
pubmed-meshheading:20884806-Receptors, Antigen, T-Cell,
pubmed-meshheading:20884806-Signal Transduction
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pubmed:year |
2010
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pubmed:articleTitle |
Loss of tonic T-cell receptor signals alters the generation but not the persistence of CD8+ memory T cells.
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pubmed:affiliation |
Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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