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Abnormal T Lymphocyte Development in Myasthenia Gravis-Associated Thymomas

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Epithelial Tumors of the Thymus

Abstract

To get an insight into the pathogenesis of thymoma-associated myasthenia gravis we studied intratumorous thymocyte maturation in different thymoma subtypes by three-colour flow cytometry. The thymocyte subset composition was characteristically altered in each histological thymoma subtype. A medullary thymoma was almost devoid of immature thymocytes and the mature intratumorous lymphocytes appeared to be mostly of peripheral origin. In contrast, mixed and cortical thymomas exhibited thymocyte development from the most immature precursor cells to cells with a pre-emigrant phenotype. These mature lymphocytes were of central origin. In mixed more than in cortical thymomas representation of immature CD4+/CD8−/CD3− thymocytes was increased although the percentage of earlier precursors was normal. A decreased production of mature CD4+ SP T cells suggests inefficient positive selection. Supporting this view, MHC class II expression was reduced on neoplastic epithelium. Inefficient generation of mature T cells in thymomas could be one reason why thymoma patients have no general defect of central tolerance. Maintåined but inefficient intratumorous T cell maturation supports the concept that abnormal positive selection of potentially autoaggressive T cells is the basis of autoimmunization in mixed and cortical thymomas. Autoimmunity in medullary thymomas might have a different pathogenesis.

Supported by grant Ma 1492/2–1 of the Deutsche Forschungsgemeinschaft (DFG) and by a grant from the “Förderungsschwerpunkt Autoimmunitätsforschung” of the German Ministry of Education and Science (BMBF)

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Authors and Affiliations

  1. Institutes of Pathology and Virology, and Department of Neurology, University of Würzburg, Josef-Schneider-Str. 2, 97080, Würzburg, Germany

    Regina Nenninger MD, Anja Schultz, Bart Vandekerckhove, Thomas Hünig, Berthold Schalke, Hans Konrad Müller-Hermelink & Alexander Marx

  2. Institute of Bacteriology and Virology, University Hospital, 9000, Gent, Belgium

    Regina Nenninger MD, Anja Schultz, Bart Vandekerckhove, Thomas Hünig, Berthold Schalke, Hans Konrad Müller-Hermelink & Alexander Marx

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  1. Regina Nenninger MD
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  1. The University of Würzburg, Würzburg, Germany

    Alexander Marx  & Hans Konrad Müller-Hermelink  & 

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Nenninger, R. et al. (1997). Abnormal T Lymphocyte Development in Myasthenia Gravis-Associated Thymomas. In: Marx, A., Müller-Hermelink, H.K. (eds) Epithelial Tumors of the Thymus. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-0033-3_23

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  • DOI: https://doi.org/10.1007/978-1-4899-0033-3_23

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