Schmitz I, Meyer C, Schulze-Osthoff K
Institute of Molecular Medicine, University of Düsseldorf, Düsseldorf, Germany.
Oncogene. 2006 Dec 7;25(58):7587-96. doi: 10.1038/sj.onc.1209741. Epub 2006 Jun 12.
Tumors in the thymus can be of different cellular origin. Among the most common tumors are thymoma and lymphoma, which are derived from transformed thymic epithelial cells and transformed lymphocytes, respectively. Thymic lymphoma and their response to apoptotic stimuli are poorly characterized. Here, we analyse apoptosis events in the thymic lymphoma cell line Thy278, which expresses cell surface antigens characteristic of immature double positive thymocytes. Upon T-cell receptor (TCR)/CD3 stimulation, Thy278 cells die by apoptosis, similar as primary thymocytes during negative selection. Caspases are crucial for deletion of both Thy278 cells and normal thymocytes. Moreover, we show that deletion of primary thymocytes and Thy278 cells upon CD3 stimulation is considerably impaired by neutralizing CD95L antibody. Thus, our results not only demonstrate that TCR-induced apoptosis is still functional in transformed thymocytes, but also suggest that Thy278 cells are a helpful model for the molecular analysis of negative selection.
胸腺肿瘤可能起源于不同的细胞。最常见的肿瘤包括胸腺瘤和淋巴瘤，它们分别来源于转化的胸腺上皮细胞和转化的淋巴细胞。胸腺淋巴瘤及其对凋亡刺激的反应目前了解甚少。在此，我们分析了胸腺淋巴瘤细胞系Thy278中的凋亡事件，该细胞系表达未成熟双阳性胸腺细胞特有的细胞表面抗原。在T细胞受体（TCR）/CD3刺激下，Thy278细胞通过凋亡死亡，这与阴性选择过程中的原代胸腺细胞类似。半胱天冬酶对于Thy278细胞和正常胸腺细胞的清除至关重要。此外，我们发现，中和CD95L抗体可显著抑制CD3刺激后原代胸腺细胞和Thy278细胞的清除。因此，我们的结果不仅表明TCR诱导的凋亡在转化的胸腺细胞中仍然起作用，还提示Thy278细胞是阴性选择分子分析的有用模型。
