Nenninger, R. and Schultz, A. and Hoffacker, V. and Helmreich, M. and Wilisch, A. and Vandekerckhove, B. and Hunig, T. and Schalke, B. and Schneider, C. and Tzartos, S. and Kalbacher, H. and Mueller-Hermelink, H. K. and Marx, A. (1998) Abnormal thymocyte development and generation of autoreactive T cells in mixed and cortical thymomas. LABORATORY INVESTIGATION, 78 (6). pp. 743-753. ISSN 0023-6837,
Full text not available from this repository.Abstract
To gain insight into the pathogenesis of thymoma-associated myasthenia gravis, thymocyte maturation was investigated in mixed and cortical thymomas by three-color flow cytometry. Although we detected cells at all recognizable stages, we noted an unusual increased percentage of early CD4(+)/CD3(-) thymocytes-especially in mixed thymoma-and a pronounced decreased percentage of mature CD4(+)/CD3(+) cells in cortical thymomas as well. The percentage of CD3(+)/CD69(+) cells that arose after positive selection was reduced in both thymoma subtypes compared with control thymuses, which suggests differences in the rate or efficiency of positive selection particularly in mixed thymomas. Mature T cells in 10 of 11 thymomas were not activated in situ as shown by the absence of CD25 expression. After stimulation with recombinant human acetylcholine receptor alpha-subunit fragments, thymocytes from 8 of 11 thymomas of both subtypes proliferated more strongly than those from controls, regardless of whether the donors were myasthenic. Responses of residual thymus cells to tetanus toroid correlated well with those of autologous blood T cells, whereas those from the thymomas clearly did not-implying minimal colonization of thymomas by mature recirculating T cells. In conclusion, our results show that cortical and mixed thymomas exhibited differences in thymocyte maturation. Nevertheless, both thymoma subtypes seem to contribute to the pathogenesis of paraneoplastic myasthenia gravis by generating naive but potentially autoaggressive T cells; in some thymomas, these cells may then be actively immunized inside the tumor.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | THYMIC EPITHELIAL TUMORS; SINGLE-POSITIVE CELLS; MYASTHENIA-GRAVIS; ACETYLCHOLINE-RECEPTOR; IMMATURE THYMOCYTES; ALPHA-SUBUNIT; CD4+8+ THYMOCYTES; LYMPHOCYTES-T; DIFFERENTIATION; SELECTION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Neurologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 09 May 2023 14:05 |
| Last Modified: | 09 May 2023 14:05 |
| URI: | https://pred.uni-regensburg.de/id/eprint/49780 |
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