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Why TAMG<\/jats:styled-content>(+) thymomas generate and export more mature CD<\/jats:styled-content>4+ T cells than MG<\/jats:styled-content>(\u2212) thymomas is unknown.<\/jats:p><\/jats:sec>Methods<\/jats:title>Unfixed thymoma tissue, thymocytes derived thereof, peripheral blood mononuclear cells (PBMC<\/jats:styled-content>s), T\u2010cell subsets and B cells were analysed using qRT<\/jats:styled-content>\u2010PCR<\/jats:styled-content> and western blotting. Survival of PBMC<\/jats:styled-content>s was measured by MTT<\/jats:styled-content> assay. FAS<\/jats:styled-content>\u2010mediated apoptosis in PBMC<\/jats:styled-content>s was quantified by flow cytometry. NF<\/jats:styled-content>\u2010\u03ba<\/jats:italic>B<\/jats:styled-content> in PBMC<\/jats:styled-content>s was inhibited by the NF<\/jats:styled-content>\u2010\u03ba<\/jats:italic>B<\/jats:styled-content>\u2010Inhibitor, EF<\/jats:styled-content>24 prior to FAS<\/jats:styled-content>\u2010Ligand (FASLG) treatment for apoptosis induction.<\/jats:p><\/jats:sec>Results<\/jats:title>Expression levels of the apoptosis inhibitor cellular FLICE\u2010like inhibitory protein (c\u2010FLIP<\/jats:styled-content>) in blood T cells and intratumorous thymocytes were higher in TAMG<\/jats:styled-content>(+) than in MG<\/jats:styled-content>(\u2212) thymomas and non\u2010neoplastic thymic remnants. Thymocytes and PBMC<\/jats:styled-content>s of TAMG<\/jats:styled-content> patients showed nuclear NF<\/jats:styled-content>\u2010\u03ba<\/jats:italic>B<\/jats:styled-content> accumulation and apoptosis resistance to FASLG stimulation that was sensitive to NF<\/jats:styled-content>\u2010\u03ba<\/jats:italic>B<\/jats:styled-content> blockade. Thymoma removal reduced cFLIP<\/jats:styled-content> expression in PBMCs.<\/jats:p><\/jats:sec>Interpretation<\/jats:title>We conclude that thymomas induce cFLIP<\/jats:styled-content> overexpression in thymocytes and their progeny, blood T cells. We suggest that the stronger cFLIP<\/jats:styled-content> overexpression in TAMG<\/jats:styled-content>(+) compared to MG<\/jats:styled-content>(\u2212) thymomas allows for the more efficient generation of mature CD<\/jats:styled-content>4+ T cells in TAMG<\/jats:styled-content>(+) thymomas. cFLIP<\/jats:styled-content> overexpression in thymocytes and exported CD<\/jats:styled-content>4+ T cells of patients with TAMG<\/jats:styled-content> might contribute to the pathogenesis of TAMG<\/jats:styled-content> by impairing central and peripheral T\u2010cell tolerance.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.210","type":"journal-article","created":{"date-parts":[[2015,7,23]],"date-time":"2015-07-23T05:09:49Z","timestamp":1437628189000},"page":"894-905","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["cFLIP<\/scp> overexpression in T cells in thymoma\u2010associated myasthenia gravis"],"prefix":"10.1002","volume":"2","author":[{"given":"Djeda","family":"Belharazem","sequence":"first","affiliation":[{"name":"Institute of Pathology University Medical Centre Mannheim, University of Heidelberg Mannheim Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berthold","family":"Schalke","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Regensburg Regensburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf","family":"Gold","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Bochum Bochum Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilfred","family":"Nix","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Mainz Mainz Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Vitacolonna","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery University Medical Centre Mannheim Mannheim Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Hohenberger","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery University Medical Centre Mannheim Mannheim Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Roessner","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery University Medical Centre Mannheim Mannheim Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Torsten. 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