Transgenic Expression of Ly-49A in Thymocytes Alters Repertoire Selection1

Transgenic Expression of Ly-49A in Thymocytes Alters Repertoire Selection1
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胸腺细胞中 Ly-49A 的转基因表达改变了库选择1

DOI:
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发表时间:
2000
影响因子:
4.4
通讯作者:
D. Lo
D. Lo
中科院分区:
医学2区
文献类型:
--
作者:
M. Pauza;Kathleen M. Smith;H. Neal;C. Reilly;L. Lanier;D. Lo

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T细胞特异性Ly-49 A转基因在H-2Dd存在下抑制TCR介导的活化。通过发育中的胸腺细胞表达这种转基因会削弱负选择,这一点可以通过未能删除潜在的自身反应性T细胞和出现移植物抗宿主疾病样综合征来证明。在携带Ly-49 A和II类限制性TCR转基因的小鼠中,阳性选择丧失,但仅当H-2Dd存在于胸腺上皮时。这些结果与表明胸腺选择依赖于TCR信号传导的感知强度的模型一致。更有趣的是,这些结果表明,Ly-49 A并不简单地为T细胞反应提供严格的开/关开关。由于Ly-49 A可以改变TCR诱导的触发的信号传导阈值,因此Ly-49 A的诱导型表达可以通过提高T细胞再活化的阈值来调节外周记忆/活化的T细胞。
A T cell-specific Ly-49A transgene inhibits TCR-mediated activation in the presence of H-2Dd. Expression of this transgene by developing thymocytes impairs negative selection evidenced by a failure to delete potentially autoreactive T cells and development of a graft-vs-host-disease-like syndrome. In mice carrying both the Ly-49A and a class II-restricted TCR transgene, positive selection was lost, but only when H-2Dd was present on thymic epithelium. These results are consistent with models suggesting that thymic selection is dependent on the perceived intensity of TCR signaling. More interestingly, these results show that Ly-49A does not simply provide a strict on/off switch for T cell responses. Since Ly-49A may shift the signaling threshold of TCR-induced triggering, inducible expression of Ly-49A may regulate peripheral memory/activated T cells by raising the threshold for T cell reactivation.
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