Inoue M, Fujii Y, Okumura M, Miyoshi S, Shiono H, Fukuhara K, Kadota Y, Matsuda H
First Department of Surgery, Osaka University Medical School, Japan.
Pathol Res Pract. 1999;195(8):541-7. doi: 10.1016/S0344-0338(99)80003-X.
Human thymoma is derived from thymic epithelial cells and often associated with a large number of cortical thymocytes. Since thymic epithelial cells play key roles in T-cell development in the normal thymus, we hypothesized that the neoplastic epithelial cells of thymoma may support T-cell differentiation. We attempted to reconstitute the T-cell development in vitro by using neoplastic epithelial cells isolated from thymoma. CD34, a stem cell marker, was expressed on a proportion of CD4-CD8- cells in thymoma. These CD34+CD4-CD8- cells also expressed both IL-7R alpha-chain and common gamma-chain. Purified CD4-CD8- cells from thymomas were cultured with the neoplastic epithelial cells, and their differentiation into CD4+CD8+ cells via CD4 single positive intermediates was observed within 9 days' co-culture in the presence of recombinant IL-7. The CD34+CD4-CD8- cells purified from a normal thymus also differentiated to CD4+CD8+ cells in an allogeneic co-culture with the neoplastic epithelial cells of thymoma. In addition, a pleural dissemination from thymoma contained a large amount of cortical thymocytes. These results suggest that the neoplastic epithelial cells retain the function of thymic epithelium and can support T-cell development in thymomas.
人类胸腺瘤起源于胸腺上皮细胞,常伴有大量皮质胸腺细胞。由于胸腺上皮细胞在正常胸腺的T细胞发育中起关键作用,我们推测胸腺瘤的肿瘤上皮细胞可能支持T细胞分化。我们试图通过使用从胸腺瘤中分离出的肿瘤上皮细胞在体外重建T细胞发育。CD34是一种干细胞标志物,在胸腺瘤中一部分CD4-CD8-细胞上表达。这些CD34+CD4-CD8-细胞还同时表达IL-7Rα链和共同γ链。将从胸腺瘤中纯化的CD4-CD8-细胞与肿瘤上皮细胞一起培养,在重组IL-7存在的情况下,共培养9天内观察到它们通过CD4单阳性中间体分化为CD4+CD8+细胞。从正常胸腺中纯化的CD34+CD4-CD8-细胞在与胸腺瘤的肿瘤上皮细胞进行异基因共培养时也分化为CD4+CD8+细胞。此外,胸腺瘤的胸膜播散中含有大量皮质胸腺细胞。这些结果表明,肿瘤上皮细胞保留了胸腺上皮的功能,并且可以支持胸腺瘤中的T细胞发育。