|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
7
|
|
pubmed:dateCreated |
2011-6-27
|
|
pubmed:abstractText |
The adaptor protein Src homology 2 domain-containing leukocyte-specific protein of 76?kDa (SLP-76) is central to the organization of intracellular signaling downstream of the T-cell receptor (TCR). Evaluation of its role in mature, primary T cells has been hampered by developmental defects that occur in the absence of WT SLP-76 protein in thymocytes. Here, we show that following tamoxifen-regulated conditional deletion of SLP-76, mature, antigen-inexperienced T cells maintain normal TCR surface expression but fail to transduce TCR-generated signals. Conditionally deficient T cells fail to proliferate in response to antigenic stimulation or a lymphopenic environment. Mice with induced deletion of SLP-76 are resistant to induction of the CD4+ T-cell-mediated autoimmune disease experimental autoimmune encephalomyelitis. Altogether, our findings demonstrate the critical role of SLP-76-mediated signaling in initiating T-cell-directed immune responses both in vitro and in vivo and highlight the ability to analyze signaling processes in mature T cells in the absence of developmental defects.
|
|
pubmed:grant |
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Jul
|
|
pubmed:issn |
1521-4141
|
|
pubmed:author |
|
|
pubmed:copyrightInfo |
Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
|
|
pubmed:issnType |
Electronic
|
|
pubmed:volume |
41
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
2064-73
|
|
pubmed:dateRevised |
2011-9-26
|
|
pubmed:meshHeading |
pubmed-meshheading:21469089-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:21469089-Animals,
pubmed-meshheading:21469089-CD4-Positive T-Lymphocytes,
pubmed-meshheading:21469089-Cell Proliferation,
pubmed-meshheading:21469089-Encephalomyelitis, Autoimmune, Experimental,
pubmed-meshheading:21469089-Flow Cytometry,
pubmed-meshheading:21469089-Mice,
pubmed-meshheading:21469089-Mice, Inbred C57BL,
pubmed-meshheading:21469089-Mice, Knockout,
pubmed-meshheading:21469089-Phosphoproteins,
pubmed-meshheading:21469089-Polymerase Chain Reaction,
pubmed-meshheading:21469089-Receptors, Antigen, T-Cell,
pubmed-meshheading:21469089-Signal Transduction,
pubmed-meshheading:21469089-T-Lymphocytes,
pubmed-meshheading:21469089-Tamoxifen
|
|
pubmed:year |
2011
|
|
pubmed:articleTitle |
Conditional deletion of SLP-76 in mature T cells abrogates peripheral immune responses.
|
|
pubmed:affiliation |
Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
|
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
|
