Inada Keiji, Okumura Meinoshin, Shiono Hiroyuki, Inoue Masayoshi, Kadota Yoshihisa, Ohta Mitsunori, Matsuda Hikaru
Department of Surgery, Division of General Thoracic Surgery, Osaka University Graduate School of Medicine, Suita-City, Osaka 565-0871, Japan.
J Surg Res. 2005 Jun 1;126(1):34-40. doi: 10.1016/j.jss.2005.01.023.
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.
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.
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.
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.
人类胸腺瘤是一种胸腺上皮肿瘤，其特征是常与重症肌无力相关。胸腺瘤的组织学特征是大量淋巴细胞共存，包括CD4(+)CD8(+)双阳性T细胞，即皮质胸腺细胞的表型。为了阐明这些T淋巴细胞在胸腺瘤相关重症肌无力发病机制中的作用，我们结合阳性选择事件研究了胸腺瘤中T淋巴细胞的αβ或γδT细胞受体的使用情况。
从28例患者中获取胸腺瘤。9例患者伴有重症肌无力。从肿瘤组织中新鲜分离淋巴细胞，并进行四色流式细胞术分析。
伴有重症肌无力的胸腺瘤中TCRαβ(+)细胞的平均比例为47.0%，显著高于无重症肌无力的胸腺瘤（23.4%）（P = 0.0008）。然后根据阳性选择标志物CD69检查阳性选择事件。重症肌无力胸腺瘤中TCRαβ(+)CD69(+)CD4(+)CD8(-)细胞的平均比例（8.22%）显著高于非重症肌无力胸腺瘤（2.99%）（P = 0.015）。另一方面，重症肌无力和非重症肌无力胸腺瘤之间TCRαβ(+)CD69(+)CD4(-)CD8(+)细胞的平均比例没有显著差异。
提示TCRαβ(+)T细胞的发育，特别是TCRαβ(+)CD4(+)CD8(-)T细胞在胸腺瘤中的阳性选择作用，在胸腺瘤相关重症肌无力的发病机制中发挥作用。
