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dc.contributor.authorHOHENBERGER, Peter
dc.contributor.authorNIX, Wilfred
dc.contributor.authorVITACOLONNA, Mario
dc.contributor.authorSaruhan-Direskeneli, Güher
dc.contributor.authorYilmaz, Vuslat
dc.contributor.authorROESSNER, Eric
dc.contributor.authorSCHULZE, Torsten. J.
dc.contributor.authorOTT, German
dc.contributor.authorSTROEBEL, Philipp
dc.contributor.authorMARX, Alexander
dc.contributor.authorBELHARAZEM, Djeda
dc.contributor.authorSCHALKE, Berthold
dc.contributor.authorGOLD, Ralf
dc.date.accessioned2021-03-02T22:21:00Z
dc.date.available2021-03-02T22:21:00Z
dc.date.issued2015
dc.identifier.citationBELHARAZEM D., SCHALKE B., GOLD R., NIX W., VITACOLONNA M., HOHENBERGER P., ROESSNER E., SCHULZE T. J. , Saruhan-Direskeneli G., Yilmaz V., et al., "cFLIP overexpression in T cells in thymoma-associated myasthenia gravis", ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY, cilt.2, sa.9, ss.894-905, 2015
dc.identifier.issn2328-9503
dc.identifier.othervv_1032021
dc.identifier.otherav_0c2cbf4c-6d19-4655-99dd-a78290a441c0
dc.identifier.urihttp://hdl.handle.net/20.500.12627/13829
dc.identifier.urihttps://doi.org/10.1002/acn3.210
dc.description.abstractObjective: The capacity of thymomas to generate mature CD4+ effector T cells from immature precursors inside the tumor and export them to the blood is associated with thymoma-associated myasthenia gravis (TAMG). Why TAMG (+) thymomas generate and export more mature CD4+ T cells than MG(-) thymomas is unknown. Methods: Unfixed thymoma tissue, thymocytes derived thereof, peripheral blood mononuclear cells (PBMCs), T-cell subsets and B cells were analysed using qRT-PCR and western blotting. Survival of PBMCs was measured by MTT assay. FAS-mediated apoptosis in PBMCs was quantified by flow cytometry. NF-kappa B in PBMCs was inhibited by the NF-kappa B-Inhibitor, EF24 prior to FAS-Ligand (FASLG) treatment for apoptosis induction. Results: Expression levels of the apoptosis inhibitor cellular FLICE-like inhibitory protein (c-FLIP) in blood T cells and intratumorous thymocytes were higher in TAMG(+) than in MG(-) thymomas and non-neoplastic thymic remnants. Thymocytes and PBMCs of TAMG patients showed nuclear NF-kappa B accumulation and apoptosis resistance to FASLG stimulation that was sensitive to NF-kappa B blockade. Thymoma removal reduced cFLIP expression in PBMCs. Interpretation: We conclude that thymomas induce cFLIP overexpression in thymocytes and their progeny, blood T cells. We suggest that the stronger cFLIP overexpression in TAMG(+) compared to MG(-) thymomas allows for the more efficient generation of mature CD4+ T cells in TAMG(+) thymomas. cFLIP overexpression in thymocytes and exported CD4+ T cells of patients with TAMG might contribute to the pathogenesis of TAMG by impairing central and peripheral T-cell tolerance.
dc.language.isoeng
dc.subjectDahili Tıp Bilimleri
dc.subjectNöroloji
dc.subjectYaşam Bilimleri
dc.subjectTemel Bilimler
dc.subjectKLİNİK NEUROLOJİ
dc.subjectTıp
dc.subjectYaşam Bilimleri (LIFE)
dc.subjectSinirbilim ve Davranış
dc.subjectNEUROSCIENCES
dc.subjectKlinik Tıp (MED)
dc.subjectKlinik Tıp
dc.subjectSağlık Bilimleri
dc.titlecFLIP overexpression in T cells in thymoma-associated myasthenia gravis
dc.typeMakale
dc.relation.journalANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
dc.contributor.departmentRuprecht Karls University Heidelberg , ,
dc.identifier.volume2
dc.identifier.issue9
dc.identifier.startpage894
dc.identifier.endpage905
dc.contributor.firstauthorID101123


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