Conditional deletion of SLP-76 in mature T cells abrogates peripheral immune responses. Eur J Immunol 2011 Jul;41(7):2064-73
Date
04/07/2011Pubmed ID
21469089Pubmed Central ID
PMC3124603DOI
10.1002/eji.201040809Scopus ID
2-s2.0-79959729423 (requires institutional sign-in at Scopus site) 13 CitationsAbstract
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.
Author List
Wu GF, Corbo E, Schmidt M, Smith-Garvin JE, Riese MJ, Jordan MS, Laufer TM, Brown EJ, Maltzman JSMESH terms used to index this publication - Major topics in bold
Adaptor Proteins, Signal TransducingAnimals
CD4-Positive T-Lymphocytes
Cell Proliferation
Encephalomyelitis, Autoimmune, Experimental
Flow Cytometry
Mice
Mice, Inbred C57BL
Mice, Knockout
Phosphoproteins
Polymerase Chain Reaction
Receptors, Antigen, T-Cell
Signal Transduction
T-Lymphocytes
Tamoxifen
