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Linker for activation of <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content> cells (<jats:styled-content style=\"fixed-case\">LAT<\/jats:styled-content>), a transmembrane adaptor protein, plays a key role in <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>\u2010cell and mast cell functions. However, it remains unclear how <jats:styled-content style=\"fixed-case\">LAT<\/jats:styled-content> may change in patients with <jats:styled-content style=\"fixed-case\">SAA<\/jats:styled-content>. This study aims at understanding the role of lymphocyte <jats:styled-content style=\"fixed-case\">LAT<\/jats:styled-content> in <jats:styled-content style=\"fixed-case\">SAA<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The expression of <jats:styled-content style=\"fixed-case\">LAT<\/jats:styled-content>, related signaling molecules, and <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>\u2010cell effector molecules was determined by flow cytometry. <jats:styled-content style=\"fixed-case\">LAT<\/jats:styled-content> m<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> was evaluated by quantitative real\u2010time <jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content>. Cytokine production by cultured T cells was determined by <jats:styled-content style=\"fixed-case\">ELISA<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Patients with <jats:styled-content style=\"fixed-case\">SAA<\/jats:styled-content> had an increased levels of <jats:styled-content style=\"fixed-case\">LAT<\/jats:styled-content> and both total phosphorylated <jats:styled-content style=\"fixed-case\">LAT<\/jats:styled-content> and of the related molecule (<jats:styled-content style=\"fixed-case\">ZAP<\/jats:styled-content>\u201070) in circulating <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content> cells compared with normal controls. In patients with <jats:styled-content style=\"fixed-case\">SAA<\/jats:styled-content>, the expression of <jats:styled-content style=\"fixed-case\">LAT<\/jats:styled-content> was positively associated with the expression of perforin and granzyme <jats:styled-content style=\"fixed-case\">B<\/jats:styled-content> in CD8<jats:sup>+<\/jats:sup> T cells. Inhibition of <jats:styled-content style=\"fixed-case\">LAT<\/jats:styled-content> expression in T cells from patients with <jats:styled-content style=\"fixed-case\">SAA<\/jats:styled-content> decreased the activation of the CD4<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup> T\u2010cell subsets. Overexpression of <jats:styled-content style=\"fixed-case\">LAT<\/jats:styled-content> in T cells from normal controls increased the activation of CD4<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup> T\u2010cell subsets with increased apoptosis of K562 cells in coculture.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our findings demonstrate that dysregulation of <jats:styled-content style=\"fixed-case\">LAT<\/jats:styled-content> expression and activation may contribute to over\u2010function of T cells, imbalance of Th1\/Th2 subsets and thus lead to hematopoiesis failure in <jats:styled-content style=\"fixed-case\">SAA<\/jats:styled-content>. Immunosuppressive therapy dramatically reduced the expression of <jats:styled-content style=\"fixed-case\">LAT<\/jats:styled-content> making it an attractive therapeutic target in SAA.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ejh.12327","type":"journal-article","created":{"date-parts":[[2014,3,27]],"date-time":"2014-03-27T12:07:07Z","timestamp":1395922027000},"page":"214-223","source":"Crossref","is-referenced-by-count":22,"title":["Abnormalities of quantities and functions of linker for activations of <scp>T<\/scp> cells in severe aplastic anemia"],"prefix":"10.1111","volume":"93","author":[{"given":"Weiwei","family":"Sheng","sequence":"first","affiliation":[{"name":"The Department of Hematology The General Hospital of Tianjin Medical University Tianjin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunyan","family":"Liu","sequence":"additional","affiliation":[{"name":"The Department of Hematology The General Hospital of Tianjin Medical University Tianjin 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