Division of Cell and Molecular Biology, Imperial College London, South Kensington Campus, London, UK.
Eur J Immunol. 2011 Jul;41(7):1924-33. doi: 10.1002/eji.201041180. Epub 2011 Jun 7.
Subsets of NK cells can have distinct functions. Here, we report that >25% of human peripheral blood NK cells express HLA-DR after culture with IL-2. This can be driven by an expansion of a small subset of NK cells expressing HLA-DR, in contrast to previous assumptions that HLA-DR is upregulated on previously negative cells. HLA-DR-expressing NK cells showed enhanced degranulation to susceptible target cells and expressed chemokine receptor CXCR3, which facilitated their enrichment following exposure to CXCL11/I-TAC. Suggesting HLA-DR-expressing NK cells have an important role in an immune response, stimulation of PBMCs with Mycobacterium bovis BCG (BCG) triggered expansion of this subset. Importantly, the magnitude of an individual's NK cell IFN-γ response triggered by BCG was associated with the initial frequency of HLA-DR-expressing NK cells in PBMCs. More directly indicating the importance of HLA-DR-expressing NK cells, enriching the frequency of this subset in PBMCs substantially augmented the IFN-γ response to BCG. Thus, HLA-DR expression marks a distinct subset of NK cells, present at low frequency in circulating blood but readily expanded by IL-2, that can play an important role during immune responses to BCG.
NK 细胞亚群可具有不同的功能。在此，我们报告，在 IL-2 培养后，超过 25%的人外周血 NK 细胞表达 HLA-DR。这可能是由一小部分表达 HLA-DR 的 NK 细胞的扩增所驱动的，与之前关于 HLA-DR 在先前阴性细胞上上调的假设相反。表达 HLA-DR 的 NK 细胞对易感性靶细胞的脱颗粒增强，并表达趋化因子受体 CXCR3，这有助于它们在暴露于 CXCL11/I-TAC 后富集。表达 HLA-DR 的 NK 细胞在免疫反应中具有重要作用，用牛分枝杆菌 BCG（BCG）刺激 PBMC 会引发该亚群的扩增。重要的是，个体的 NK 细胞 IFN-γ 反应被 BCG 触发的程度与 PBMC 中表达 HLA-DR 的 NK 细胞的初始频率相关。更直接表明表达 HLA-DR 的 NK 细胞的重要性，在 PBMC 中富集该亚群的频率可显著增强对 BCG 的 IFN-γ 反应。因此，HLA-DR 表达标志着 NK 细胞的一个独特亚群，在外周循环血液中的频率较低，但可通过 IL-2 容易地扩增，在对 BCG 的免疫反应中可发挥重要作用。
