Generation of Novel Traj18-Deficient Mice Lacking Vα14 Natural Killer T Cells with an Undisturbed T Cell Receptor α-Chain Repertoire.
Generation of Novel Traj18-Deficient Mice Lacking Vα14 Natural Killer T Cells with an Undisturbed T Cell Receptor α-Chain Repertoire.
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DOI：
10.1371/journal.pone.0153347
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Taniguchi M
中科院分区：
文献类型：
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作者：
Dashtsoodol N;Shigeura T;Ozawa R;Harada M;Kojo S;Watanabe T;Koseki H;Nakayama M;Ohara O;Taniguchi M
不变Vα14自然杀伤T（NKT）细胞，其特征为在小鼠中表达由重排的Trav 11（Vα14）-Traj 18（Jα18）基因片段编码的单一不变T细胞受体（TCR）α链，在人体中表达TRAV 10（Vα24）-TRAJ 18（Jα18），介导佐剂作用以激活先天性和适应性免疫系统中的各种效应细胞类型，从而促进有效的抗肿瘤作用。最近有报道称，我们的小组在1997年描述的Jα18缺陷小鼠具有受干扰的TCRα库，这引起了人们对使用该小鼠系得出的一些实验结论的有效性的担忧。为了解决这个问题，我们通过使用Cre-Lox方法特异性靶向Traj 18基因片段产生了一种新的Traj 18缺陷小鼠系。在这里，我们通过使用下一代测序和检测表达Vα 19 J α33的粘膜相关不变T细胞的正常代（其发育在最初描述的Jα18-KO小鼠中被废除），表明新产生的Traj 18缺陷小鼠除了缺乏Traj 18外，还具有未受干扰的TCRα链库。我们还证明了NKT细胞在抗肿瘤保护中的明确需求及其对抗原特异性CD 8 T细胞的有效佐剂作用。
Invariant Vα14 natural killer T (NKT) cells, characterized by the expression of a single invariant T cell receptor (TCR) α chain encoded by rearranged Trav11 (Vα14)-Traj18 (Jα18) gene segments in mice, and TRAV10 (Vα24)-TRAJ18 (Jα18) in humans, mediate adjuvant effects to activate various effector cell types in both innate and adaptive immune systems that facilitates the potent antitumor effects. It was recently reported that the Jα18-deficient mouse described by our group in 1997 harbors perturbed TCRα repertoire, which raised concerns regarding the validity of some of the experimental conclusions that have been made using this mouse line. To resolve this concern, we generated a novel Traj18-deficient mouse line by specifically targeting the Traj18 gene segment using Cre-Lox approach. Here we showed the newly generated Traj18-deficient mouse has, apart from the absence of Traj18, an undisturbed TCRα chain repertoire by using next generation sequencing and by detecting normal generation of Vα19Jα33 expressing mucosal associated invariant T cells, whose development was abrogated in the originally described Jα18-KO mice. We also demonstrated here the definitive requirement for NKT cells in the protection against tumors and their potent adjuvant effects on antigen-specific CD8 T cells.