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

J Surg Res. 2005 Jun 1;126(1):34-40. doi: 10.1016/j.jss.2005.01.023.

Abstract

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 alphabeta or gammadelta 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 TCRalphabeta(+) 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 TCRalphabeta(+)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 TCRalphabeta(+)CD69(+)CD4(-)CD8(+) cells between the myasthenic and the nonmyasthenic thymomas.

Conclusions: The possible role of development of TCRalphabeta(+) T cells, especially the role of positive selection of TCRalphabeta(+)CD4(+)CD8(-) T cells in thymoma, was suggested in the pathogenesis of thymoma-associated myasthenia gravis.

MeSH terms

  • Adult
  • Aged
  • Antigens, CD / analysis
  • Antigens, CD1 / analysis
  • Antigens, Differentiation, T-Lymphocyte / analysis
  • Cell Lineage
  • Female
  • Humans
  • Lectins, C-Type
  • Male
  • Middle Aged
  • Myasthenia Gravis / etiology*
  • Myasthenia Gravis / immunology
  • Receptors, Antigen, T-Cell, alpha-beta / analysis
  • Receptors, Antigen, T-Cell, gamma-delta / analysis
  • T-Lymphocytes / immunology*
  • Thymoma / immunology*

Substances

  • Antigens, CD
  • Antigens, CD1
  • Antigens, Differentiation, T-Lymphocyte
  • CD1a antigen
  • CD69 antigen
  • Lectins, C-Type
  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, Antigen, T-Cell, gamma-delta