Cutting Edge: Identification and Characterization of Human Intrahepatic CD49a+ NK Cells
Cutting Edge: Identification and Characterization of Human Intrahepatic CD49a+ NK Cells
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DOI：
10.4049/jimmunol.1402756
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发表时间：
2015-03-15
影响因子：
4.4
通讯作者：
Bjorkstrom, Niklas K.
中科院分区：
文献类型：
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作者：
Marquardt, Nicole;Beziat, Vivien;Bjorkstrom, Niklas K.
尽管NK细胞被认为是与生俱来的，但最近在小鼠身上的研究表明，肝CD49a(+)DX5(-)NK细胞存在一个独特的谱系，具有适应性样特征。与传统的NK细胞不同，这种NK细胞系的发展依赖于T-bet，而不是Eome。在这项研究中，我们描述了T-bet(+)eome(-)CD49a(+)NK细胞亚群在人的肝脏中很容易检测到，但在传入或传出肝静脉或外周血中不能检测到。人肝内CD49a(+)NK细胞表达杀伤细胞Ig样受体和NKG2C，提示经历了克隆样扩增，CD56(明亮)，低水平表达CD16、CD57和穿孔素。刺激后，CD49a(+)NK细胞表达高水平的炎性细胞因子，但脱颗粒较少。CD49a(+)NK细胞在体外长期扩增后仍保持其表型。这些结果表明，小鼠肝内NK细胞可能存在人类对应物，具有适应性样特征。
Although NK cells are considered innate, recent studies in mice revealed the existence of a unique lineage of hepatic CD49a(+)DX5(-) NK cells with adaptive-like features. Development of this NK cell lineage is, in contrast to conventional NK cells, dependent on T-bet but not Eomes. In this study, we describe the identification of a T-bet(+)Eomes(-)CD49a(+) NK cell subset readily detectable in the human liver, but not in afferent or efferent hepatic venous or peripheral blood. Human intrahepatic CD49a(+) NK cells express killer cell Ig-like receptor and NKG2C, indicative of having undergone clonal-like expansion, are CD56(bright), and express low levels of CD16, CD57, and perforin. After stimulation, CD49a(+) NK cells express high levels of inflammatory cytokines but degranulate poorly. CD49a(+) NK cells retain their phenotype after expansion in long-term in vitro cultures. These results demonstrate the presence of a likely human counterpart of mouse intrahepatic NK cells with adaptive-like features.