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  • Title: [Abnormal T cell maturation in myasthenia gravis associated thymomas].
    Author: Nenninger R, Schultz A, Müller-Hermelink HK, Marx A.
    Journal: Verh Dtsch Ges Pathol; 1996; 80():256-60. PubMed ID: 9065022.
    Abstract:
    AIMS AND METHODS: Paraneoplastic myasthenia gravis is a thymoma-associated autoimmune disease, characterized by autoantibodies against the acetylcholine receptor (AChR). CD4+ AChR-specific T cells play a pivotal role in the production of autoantibodies. However, it is not known how the tumor is involved in the pathogenesis of autoimmunity. To address this question thymocyte maturation was followed in medullary, mixed and cortical thymomas using three-color FACS analysis. RESULTS: Compared to normal thymuses medullary thymomas were almost devoid of immature T cells and most intratumorous lymphocytes appeared to be of peripheral origin. In mixed and cortical thymomas maturation of thymocytes took place from the most immature precursors to thymomcytes with a mature phenotype. Only in the latter tumor subtypes immature CD4+/CD8-/CD3-thymocytes were significantly increased. In addition, a reduced production of mature CD4+ T cells suggests ineffective positive selection. Activated T cells were present in one medullary but none of the mixed or cortical thymomas. CONCLUSION: Each histological thymoma subtype is associated with a characteristic defect of T cell maturation. The contribution of medullary thymomas to the pathogenesis of myasthenia gravis (MG) might be a pathological intratumorous T cell activation. By contrast, an abnormal antigen-specific T cell selection may be the contribution of cortical and mixed thymomas to anti-AChR autoimmunity.
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