Belharazem, Djeda and Schalke, Berthold and Gold, Ralf and Nix, Wilfred and Vitacolonna, Mario and Hohenberger, Peter and Roessner, Eric and Schulze, Torsten. J. and Saruhan-Direskeneli, Gueher and Yilmaz, Vuslat and Ott, German and Stroebel, Philipp and Marx, Alexander (2015) cFLIP overexpression in T cells in thymoma-associated myasthenia gravis. ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY, 2 (9). pp. 894-905. ISSN 2328-9503,
Full text not available from this repository. (Request a copy)Abstract
Objective: 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | EVIDENCE-BASED PATHOLOGY; ACETYLCHOLINE-RECEPTOR; INHIBITORY PROTEIN; MUCOCUTANEOUS CANDIDIASIS; AUTOIMMUNE-DISEASE; DIAGNOSTIC-VALUE; SELF-TOLERANCE; CLASS-II; APOPTOSIS; CD4(+); |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Neurologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 07 Jun 2019 12:34 |
| Last Modified: | 07 Jun 2019 12:34 |
| URI: | https://pred.uni-regensburg.de/id/eprint/4855 |
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