INSERM Unité Mixte de Recherche-S 945, Hôpital Pitié-Salpêtrière, 75013 Paris, France.
J Immunol. 2011 Jun 15;186(12):6753-61. doi: 10.4049/jimmunol.1100330. Epub 2011 May 9.
Human NK cells comprise two main subsets, CD56(bright) and CD56(dim) cells, which differ in function, phenotype, and tissue localization. To further dissect the differentiation from CD56(bright) to CD56(dim) cells, we performed ex vivo and in vitro experiments demonstrating that the CD56(bright)CD16(+) cells are an intermediate stage of NK cell maturation. We observed that the maximal frequency of the CD56(bright)CD16(+) subset among NK cells, following unrelated cord blood transplantation, occurs later than this of the CD56(bright)CD16(-) subset. We next performed an extensive phenotypic and functional analysis of CD56(bright)CD16(+) cells in healthy donors, which displayed a phenotypic intermediary profile between CD56(bright)CD16(-) and CD56(dim)CD16(+) NK cells. We also demonstrated that CD56(bright)CD16(+) NK cells were fully able to kill target cells, both by Ab-dependent cell cytotoxicity (ADCC) and direct lysis, as compared with CD56(bright)CD16(-) cells. Importantly, in vitro differentiation experiments revealed that autologous T cells specifically encourage the differentiation from CD56(bright)CD16(-) to CD56(bright)CD16(+) cells. Finally, further investigations performed in elderly patients clearly showed that both CD56(bright)CD16(+) and CD56(dim)CD16(+) mature subsets were substantially increased in older individuals, whereas the CD56(bright)CD16(-) precursor subset was decreased. Altogether, these data provide evidence that the CD56(bright)CD16(+) NK cell subset is a functional intermediate between the CD56(bright) and CD56(dim) cells and is generated in the presence of autologous T CD3(+) cells.
人类自然杀伤 (NK) 细胞包括两个主要亚群，即 CD56(bright) 和 CD56(dim) 细胞，它们在功能、表型和组织定位上有所不同。为了进一步剖析从 CD56(bright) 到 CD56(dim) 细胞的分化过程，我们进行了体外和体内实验，结果表明 CD56(bright)CD16(+) 细胞是 NK 细胞成熟的一个中间阶段。我们观察到，在无关脐带血移植后，NK 细胞中 CD56(bright)CD16(+) 亚群的最大频率出现时间晚于 CD56(bright)CD16(-) 亚群。接下来，我们对健康供体中的 CD56(bright)CD16(+) 细胞进行了广泛的表型和功能分析，结果显示其表型处于 CD56(bright)CD16(-) 和 CD56(dim)CD16(+) NK 细胞之间。我们还证明，与 CD56(bright)CD16(-) 细胞相比，CD56(bright)CD16(+) NK 细胞能够通过抗体依赖性细胞毒性 (ADCC) 和直接溶解充分杀伤靶细胞。重要的是，体外分化实验表明，自体 T 细胞可特异性促进 CD56(bright)CD16(-) 向 CD56(bright)CD16(+) 细胞的分化。最后，在老年患者中进行的进一步研究清楚地表明，在老年人中，CD56(bright)CD16(+) 和 CD56(dim)CD16(+) 成熟亚群显著增加，而 CD56(bright)CD16(-) 前体细胞亚群减少。综上所述，这些数据表明 CD56(bright)CD16(+) NK 细胞亚群是 CD56(bright) 和 CD56(dim) 细胞之间的功能性中间产物，并且是在自体 T CD3(+) 细胞存在的情况下产生的。
