CD1d-unrestricted NKT cells are endowed with a hybrid function far superior than that of iNKT cells
CD1d-unrestricted NKT cells are endowed with a hybrid function far superior than that of iNKT cells
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DOI：
10.1073/pnas.1323405111
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发表时间：
2014-09-02
影响因子：
11.1
通讯作者：
Laouar, Yasmina
中科院分区：
文献类型：
--
作者：
Farr, Alexander R.;Wu, Weisheng;Laouar, Yasmina
到目前为止，不变自然杀伤T细胞(INKT)代表了已知的具有混合功能的细胞的最佳例子，代表了先天免疫和获得性免疫。与NK细胞共有的表型相似性、对细胞因子刺激的快速反应以及高效的TCR参与是iNKT细胞杂交本质的突出特征。利用这些标准，我们提供了分子和功能证据，证明CD1d非依赖性(CD1d(Ind))NKT细胞被赋予远优于iNKT细胞的杂交功能：(I)与NK细胞广泛共享程序，(Ii)与NK细胞更近的欧几里得距离，(Iii)以与NK细胞相同的方式对具有细胞毒性潜力的先天刺激(Poly：IC)做出反应的能力，鉴定CD1d(Ind)NKT细胞具有真正实现NK和T细胞双重功能的杂交特征。我们的发现是，CD1d(Ind)NKT细胞被编程为在响应天然信号的同时具有适应反应的NK细胞，这是史无前例的，因此可能会再次强调CD1d-非限制性NKT细胞作为淋巴细胞的一个子集，可能以一种独特的方式影响抗菌和肿瘤免疫的生物学过程。
Invariant natural killer T (iNKT) cells to date represent the best example of cells known to have a hybrid function, representing both innate and adaptive immunity. Shared phenotypic similarities with NK cells together with a rapid response to a cytokine stimulus and a productive TCR engagement are the features that underline the hybrid nature of iNKT cells. Using these criteria, we provide molecular and functional evidence demonstrating that CD1d-independent (CD1d(ind)) NKT cells, a population of CD1d-unrestricted NKT cells, are endowed with a hybrid function far superior to that of iNKT cells: (i) an extensive shared program with NK cells, (ii) a closer Euclidian distance with NK cells, and (iii) the ability to respond to innate stimuli (Poly:IC) with cytotoxic potential in the same manner as NK cells identify a hybrid feature in CD1d(ind)NKT cells that truly fulfills the dual function of an NK and a T cell. Our finding that CD1d(ind)NKT cells are programmed to act like NK cells in response to innate signals while being capable of adaptive responses is unprecedented, and thus might reemphasize CD1d-unrestricted NKT cells as a subset of lymphocytes that could affect biological processes of antimicrobial and tumor immunity in a unique way.