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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
1997-8-14
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pubmed:abstractText |
CD28 is a cell surface molecule that mediates a costimulatory signal crucial for T cell proliferation and lymphokine production. The signal transduction mechanisms of CD28 are not well understood. Itk, a nonreceptor protein tyrosine kinase specifically expressed in T cells and mast cells, has been implicated in the CD28 signaling pathway because of reports that it becomes phosphorylated on tyrosines and associates with CD28 upon cross-linking of the cell surface molecule. To determine whether Itk plays a functional role in CD28 signaling, we compared T cells from Itk-deficient mice and control mice for their responses to CD28 costimulation. T cells defective in Itk were found to be fully competent to respond to costimulation. Whereas the CD3-mediated proliferative response was severely compromised in the absence of Itk, the calcineurin-independent CD28-mediated response was significantly elevated when compared with cells from control animals. The augmented proliferation was not due to increased production of interleukin-2. The results suggest that Itk has distinct roles in the CD3 versus the CD28 signaling pathways. By negatively regulating the amplitude of signaling upon CD28 costimulation, Itk may provide a means for modulating the outcome of T cell activation during development and during antigen-driven immune responses.
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pubmed:grant |
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0022-1007
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
21
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pubmed:volume |
186
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
221-8
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:9221751-Animals,
pubmed-meshheading:9221751-Antigens, CD28,
pubmed-meshheading:9221751-Interleukin-2,
pubmed-meshheading:9221751-Lymphocyte Activation,
pubmed-meshheading:9221751-Mice,
pubmed-meshheading:9221751-Mice, Inbred C57BL,
pubmed-meshheading:9221751-Protein-Tyrosine Kinases,
pubmed-meshheading:9221751-Receptors, Antigen, T-Cell,
pubmed-meshheading:9221751-Signal Transduction,
pubmed-meshheading:9221751-T-Lymphocytes
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pubmed:year |
1997
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pubmed:articleTitle |
Itk negatively regulates induction of T cell proliferation by CD28 costimulation.
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pubmed:affiliation |
Department of Microbiology and Immunology, University of California, San Francisco, California 94143, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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