Abnormal T Lymphocyte Development in Myasthenia Gravis-Associated Thymomas

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


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.


Thymic Carcinoma Double Positive Thymic Epithelial Tumor Normal Thymus Single Positive 
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Copyright information

© Springer Science+Business Media New York 1997

Authors and Affiliations

  • Regina Nenninger
    • 1
    • 2
  • Anja Schultz
    • 1
    • 2
  • Bart Vandekerckhove
    • 1
    • 2
  • Thomas Hünig
    • 1
    • 2
  • Berthold Schalke
    • 1
    • 2
  • Hans Konrad Müller-Hermelink
    • 1
    • 2
  • Alexander Marx
    • 1
    • 2
  1. 1.Institutes of Pathology and Virology, and Department of NeurologyUniversity of WürzburgWürzburgGermany
  2. 2.Institute of Bacteriology and VirologyUniversity HospitalGentBelgium

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