Wendt Katy, Wilk Esther, Buyny Sabine, Buer Jan, Schmidt Reinhold E, Jacobs Roland
Department of Clinical Immunology, OE 6830, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover D-30625, Germany.
J Leukoc Biol. 2006 Dec;80(6):1529-41. doi: 10.1189/jlb.0306191. Epub 2006 Sep 11.
Recent findings underline the role of NK cell subsets in regulating adaptive immunity. To define characteristics of NK cell subpopulations, purified CD56(dim) and CD56(bright) NK cells were analyzed by using gene chip arrays covering more than 39,000 transcripts. Gene profiling revealed resting NK cells to differ in respect to 473 transcripts with 176 exclusively expressed in CD56(dim) and 130 solely in CD56(bright) NK cells. Results were compared with array analyses using mRNA obtained from activated CD56(dim) and CD56(bright) NK cells. In this approach, NK cell receptors, cytolytic molecules, adhesion structures, and chemokine ligands showed differential expression patterns in the two subpopulations. These data were validated using FACS, RT-qPCR, or cytokine bead array (CBA) techniques. Cytokines produced by CD56(dim) and CD56(bright) NK cells were determined using a protein array covering 79 different bioactive mediators. GDNF, IGFBP-1, EGF, and TIMP-2 were detected in both subsets. In contrast, IGFBP-3 and IGF-1 were mainly produced by CD56(dim), while GM-CSF, TARC, and TGFbeta3 were expressed by CD56(bright) NK cells. In summary, we report new characteristic features of CD56(dim) and CD56(bright) NK cells, further underscoring that they represent independent populations with functionally diverse capabilities. The information on NK cells generated in this study will help to define corresponding NK cell populations in other species that lack CD56 expression on NK cells, such as mice. This will subsequently lead to the establishment of suitable animal models for detailed analysis of NK cell populations in vivo.
近期研究结果突显了自然杀伤（NK）细胞亚群在调节适应性免疫中的作用。为了明确NK细胞亚群的特征，利用覆盖超过39,000个转录本的基因芯片阵列对纯化的CD56（dim）和CD56（bright）NK细胞进行了分析。基因谱分析显示，静息NK细胞在473个转录本方面存在差异，其中176个仅在CD56（dim）NK细胞中表达，130个仅在CD56（bright）NK细胞中表达。将结果与使用从活化的CD56（dim）和CD56（bright）NK细胞获得的mRNA进行的阵列分析进行了比较。在这种方法中，NK细胞受体、溶细胞分子、黏附结构和趋化因子配体在这两个亚群中呈现出不同的表达模式。这些数据通过荧光激活细胞分选（FACS）技术、逆转录定量聚合酶链反应（RT-qPCR）技术或细胞因子珠阵列（CBA）技术进行了验证。使用覆盖79种不同生物活性介质的蛋白质阵列测定了CD56（dim）和CD56（bright）NK细胞产生的细胞因子。在两个亚群中均检测到胶质细胞源性神经营养因子（GDNF）、胰岛素样生长因子结合蛋白-1（IGFBP-1）、表皮生长因子（EGF）和金属蛋白酶组织抑制因子-2（TIMP-2）。相比之下，IGFBP-3和胰岛素样生长因子-1（IGF-1）主要由CD56（dim）NK细胞产生，而粒细胞-巨噬细胞集落刺激因子（GM-CSF）、胸腺和活化调节趋化因子（TARC）以及转化生长因子β3（TGFbeta3）则由CD56（bright）NK细胞表达。总之，我们报告了CD56（dim）和CD56（bright）NK细胞的新特征，进一步强调它们代表了具有功能多样性的独立群体。本研究中生成的关于NK细胞的信息将有助于确定其他在NK细胞上缺乏CD56表达的物种（如小鼠）中的相应NK细胞群体。这随后将导致建立合适的动物模型，用于在体内详细分析NK细胞群体。
