NKG2D performs two functions in invariant NKT cells: Direct TCR-independent activation of NK-like cytolysis and co-stimulation of activation by CD1d
NKG2D performs two functions in invariant NKT cells: Direct TCR-independent activation of NK-like cytolysis and co-stimulation of activation by CD1d
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DOI：
10.1002/eji.200940278
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发表时间：
2011-07-01
影响因子：
5.4
通讯作者：
Sandberg, Johan K.
中科院分区：
文献类型：
--
作者：
Kuylenstierna, Carlotta;Bjorkstrom, Niklas K.;Sandberg, Johan K.
不变的NKT细胞在免疫反应的激活和调节中是重要的。它们也可以作为cd1限制性杀伤细胞。然而，激活NKT细胞上表达的先天nk细胞受体在触发细胞溶解功能中的作用尚不清楚。在这里，我们初步证实细胞应激配体受体NKG2D在CD4(-) NKT细胞上表达，而大多数CD4(+) NKT细胞缺乏这种受体。有趣的是，NKG2D - 1 NKT细胞频繁表达穿孔素，并且NKG2D和穿孔素都定位于与表达NKG2D配体的靶细胞接触的部位。在一项重定向激活试验中，CD4(-) NKT细胞对NKG2D参与的脱颗粒反应独立于通过其不变的TCR刺激。NKT细胞以nkg2d依赖的方式杀死抗nkg2d单抗包被的P815细胞和cd1阴性的K562肿瘤靶细胞。此外，NKG2D参与共同刺激了tcr介导的nkt细胞激活，以响应内源性cd1配体或次优水平的抗cd3触发。这些数据表明，人类NKT细胞的CD4（-）亚群可以通过独立于CD1d的NKG2D参与介导靶细胞的直接裂解，并且NKG2D也在这些细胞中作为共刺激受体发挥作用。因此，NKG2D在NKT细胞的激活中起直接和共刺激作用。
Invariant NKT cells are important in the activation and regulation of immune responses. They can also function as CD1d-restricted killer cells. However, the role of activating innate NK-cell receptors expressed on NKT cells in triggering cytolytic function is poorly characterized. Here, we initially confirmed that the cellular stress-ligand receptor NKG2D is expressed on CD4(-) NKT cells, whereas most CD4(+) NKT cells lack this receptor. Interestingly, NKG2D 1 NKT cells frequently expressed perforin, and both NKG2D and perforin localized at the site of contact with NKG2D ligand-expressing target cells. CD4(-) NKT cells degranulated in response to NKG2D engagement in a redirected activation assay independent of stimulation via their invariant TCR. NKT cells killed P815 cells coated with anti-NKG2D mAb and CD1d-negative K562 tumor target cells in an NKG2D-dependent manner. Furthermore, NKG2D engagement co-stimulated TCR-mediated NKT-cell activation in response to endogenous CD1d-presented ligands or suboptimal levels of anti-CD3 triggering. These data indicate that the CD4(-) subset of human NKT cells can mediate direct lysis of target cells via NKG2D engagement independent of CD1d, and that NKG2D also functions as a co-stimulatory receptor in these cells. NKG2D thus plays both a direct and a co-stimulatory role in the activation of NKT cells.