Transgenic expression of a novel thymic epithelial cell antigen stimulates abberant development of thymocytes.
Transgenic expression of a novel thymic epithelial cell antigen stimulates abberant development of thymocytes.
复制标题
新型胸腺上皮细胞抗原的转基因表达刺激胸腺细胞的异常发育。
DOI：
--
复制
发表时间：
1997
影响因子：
4.4
通讯作者：
Hiroshi Yamamoto
中科院分区：
文献类型：
--
作者：
T. Takeuchi;M. Kuro;H. Miyazawa;Y. Ohtsuki;Hiroshi Yamamoto
我们以前报道了一种新的胸腺基质细胞抗原，HS 9，作为一个有效的分子参与胸腺内T细胞的发展。HS 9 Ag在胸腺基质细胞上表达，特别是在皮质中，但在胸腺细胞上不表达。在本研究中，我们分离和鉴定了一个新的cDNA，N14，编码HS 9 Ag。N14 cDNA序列分析表明，它是一个新的功能分子，与以前报道的功能分子没有任何显着的同源性。用携带N14 cDNA的表达载体转染的COS 7细胞变得与HS 9特异性mAb反应。北方印迹分析和原位杂交显示，几个组织中的HS 9 mAb阳性表达N14 mRNA。为了研究这种分子在T细胞发育中的作用，产生了转基因小鼠。原位杂交和免疫组织化学研究表明，转基因在胸腺皮质和髓质基质细胞上均显著过表达，但在胸腺细胞上不表达。流式细胞术分析表明，成熟的CD 4-CD 8+或CD 4 + CD 8-胸腺细胞的百分比在转基因小鼠的约两倍和三倍，分别是那些在对照同窝。此外，与外周T细胞相比，大量的CD 4 + CD 8+胸腺细胞似乎具有高水平的TCR。组织学检查显示，转基因小鼠皮质较薄，髓质相对发达。这些数据表明N14基因在T细胞发育中的关键作用。
We previously reported a novel thymic stromal cell Ag, HS9, as a potent molecule participating in intrathymic T cell development. HS9 Ag is expressed on thymic stromal cells especially in the cortex but not on thymocytes. In the present study, we isolated and characterized a novel cDNA, N14, encoding HS9 Ag. Sequencing analysis of N14 cDNA has revealed it to be a novel one without any significant homology to previously reported functional molecules. COS7 cells transfected with expression vectors harboring N14 cDNA became reactive with HS9-specific mAb. Northern blot analysis and in situ hybridization revealed that several tissues that are positive for HS9 mAb expressed N14 mRNA. To examine the role of this molecule in T cell development, transgenic mice were generated. In situ hybridization and immunohistochemical study showed that the transgene was significantly overexpressed on both cortical and medullar thymic stromal cells but not on thymocytes. Flow cytometric analyses showed that the percentages of mature CD4- CD8+ or CD4+ CD8- thymocytes in transgenic mice were approximately twice and triple, respectively, those in control littermates. Moreover, substantial CD4+ CD8+ thymocytes appeared to have high levels of TCR compared with peripheral T cells. Histologic examination revealed that transgenic mice had thin cortex and relatively developed medulla. These data indicate the critical role of the N14 gene in T cell development.