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 alphabeta or gammadelta T cell receptor of the T lymphocytes in thymoma in conjunction with the positive selection event.


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.
Inada
Keiji
K
Department of Surgery, Division of General Thoracic Surgery, Osaka University Graduate School of Medicine, Suita-City, Osaka 565-0871, Japan.
Okumura
Meinoshin
M
Shiono
Hiroyuki
H
Inoue
Masayoshi
M
Kadota
Yoshihisa
Y
Ohta
Mitsunori
M
Matsuda
Hikaru
H
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D018949:Antigens, CD1 / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D019070:Cell Lineage; D005260:Female; D006801:Humans; D037181:Lectins, C-Type; D008297:Male; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000209:etiology* / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology*; D013945:Thymoma / Q000276:immunology*; D000099192:CD69 Antigens
D015703:Antigens, CD; D018949:Antigens, CD1; D000945:Antigens, Differentiation, T-Lymphocyte; D037181:Lectins, C-Type; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D000099192:CD69 Antigens; C419393:CD1a antigen