Role of positive selection of thymoma-associated T cells in the pathogenesis of myasthenia gravis

Background. A human thymoma is a thymic epithelial neoplasm and is characterized by its frequent association with myasthenia gravis. The histological characteristic of thymoma is coexistence of a large number of lymphocytes, including CD4(+)CD8(+) double positive T cells, phenotypes of the cortical thymocytes. To elucidate the role of these T lymphocytes in the pathogenesis of thymoma-associated myasthenia gravis, we examined the usage of alpha beta gamma delta T cell receptor of the T lymphocytes in thymoma in conjunction with the positive selection event. Materials and Methods. Thymomas were obtained from 28 patients. Nine patients were associated with myasthenia gravis. Lymphocytes were freshly isolated from the tumor tissue and were subjected to four-color flow cytometric analysis. Results. The average proportion of TCR alpha beta(+) cells in thymomas associated with myasthenia gravis was 47.0% and was significantly higher (P = 0.0008) than that without myasthenia gravis (23.4%). Positive selection event was then examined in terms of CD69, a positive selection marker. The mean proportion of TCR alpha beta(+)CD69(+)CD4(+)CD8(-) cells in the myasthenic thymomas (8.22%) was significantly greater (P = 0.015) than the nonmyasthenic thymomas (2.99%). On the other hand, there was not a significant difference in the mean proportion of TCR alpha beta(+)CD69(+)CD4(-)CD8(+) cells between the myasthenic and the nonmyasthenic thymomas. Conclusions. The possible role of development of TCR alpha beta(+) T cells, especially the role of positive selection of TCR alpha beta(+)CD4(+)CD8(-) T cells in thymoma, was suggested in the pathogenesis of thymoma-associated myasthenia gravis. (C) 2005 Elsevier Inc. All rights reserved.