Intrathymic NKT cell development is blocked by the presence of alpha-galactosylceramide.
Intrathymic NKT cell development is blocked by the presence of alpha-galactosylceramide.
复制标题
α-半乳糖神经酰胺的存在会阻碍胸腺内 NKT 细胞的发育。
DOI：
10.1080/10926771.2011.586400
复制
发表时间：
2003
影响因子：
5.4
通讯作者：
D. Godfrey
中科院分区：
文献类型：
--
作者：
D. Pellicci;Adam P. Uldrich;K. Kyparissoudis;N. Crowe;A. Brooks;Kirsten J. L. Hammond;S. Sidobre;M. Kronenberg;M. Smyth;D. Godfrey
NKT细胞发育发生在胸腺中，开始于这些细胞在表达Va 14 J α 18 T细胞受体（TCR）和识别CD 1d分子后从CD 4 + CD 8+主流胸腺细胞中分支出来。虽然NKT细胞表达不变的TCR α链，但TCR β表达的多样性使这些细胞的发育有可能是在CD 1d的背景下通过糖脂抗原识别形成的。在这里，我们表明，激动剂糖脂配体，α-半乳糖神经酰胺的存在下，而NKT细胞在体外或体内开发，特别是消融他们的发展。相反，在NKT细胞发育后，在体外或体内延迟引入该化合物不会耗尽这些细胞。这些数据表明，NKT细胞通过一个发育窗口，在那里它们对TCR介导的阴性选择敏感，并表明具有潜在高水平自身反应性的NKT细胞可以在它们离开胸腺之前从NKT细胞库中去除。
NKT cell development takes place in the thymus, beginning when these cells branch away from CD4+CD8+ mainstream thymocytes upon expression of the Valpha14Jalpha18 T cell receptor (TCR) and recognition of the CD1d molecule. Although NKT cells express an invariant TCR alpha chain, the diverse TCR beta expression leaves open the possibility that the development of these cells is shaped by glycolipid antigen recognition in the context of CD1d. Here, we show that the presence of an agonist glycolipid ligand, alpha-galactosylceramide, while NKT cells are developing in vitro or in vivo, specifically ablates their development. In contrast, the delayed introduction of this compound in vitro or in vivo, after NKT cells have developed, does not deplete these cells. These data indicate that NKT cells pass through a developmental window where they are susceptible to TCR-mediated negative selection, and suggest that NKT cells with a potentially high level of self reactivity can be removed from the NKT cell repertoire before they exit the thymus.