Department for Immunology, Leibniz Research Centre for Working Environment and Human Factors (IfADo) at TU Dortmund, Dortmund, Germany.
Eur J Immunol. 2020 May;50(5):656-665. doi: 10.1002/eji.201948344. Epub 2020 Feb 19.
Natural Killer (NK) cell responses are regulated by a variety of different surface receptors. While we can determine the overall positive or negative effect of a given receptor on NK cell functions, investigating NK cell regulation in a quantitative way is challenging. To quantitatively investigate individual receptors for their effect on NK cell activation, we chose to functionalize latex beads that have approximately the same size as lymphocytes with defined amounts of specific antibodies directed against distinct activating receptors. This enabled us to investigate NK cell reactivity in a defined, clean, and controllable system. Only CD16 and NKp30 could activate the degranulation of resting human NK cells. CD16, NKG2D, NKp30, NKp44, and NKp46 were able to activate cultured NK cells. NK cell activation resulted in the induction of polyfunctional cells that degranulated and produced IFN-γ and MIP-1β. Interestingly, polyfunctional NK cells were only induced by triggering ITAM-coupled receptors. NKp44 showed a very sensitive response pattern, where a small increase in receptor stimulation caused maximal NK cell activity. In contrast, stimulation of 2B4 induced very little NK cell degranulation, while providing sufficient signal for NK cell adhesion. Our data demonstrate that activating receptors differ in their effectiveness to stimulate NK cells.
自然杀伤 (NK) 细胞的反应受多种不同的表面受体调节。虽然我们可以确定给定受体对 NK 细胞功能的总体正或负影响，但以定量方式研究 NK 细胞的调节具有挑战性。为了定量研究单个受体对 NK 细胞激活的影响，我们选择用具有特定抗体的乳胶珠对淋巴细胞进行功能化，这些抗体针对不同的激活受体，且数量确定。这使我们能够在一个明确、清洁和可控的系统中研究 NK 细胞的反应性。只有 CD16 和 NKp30 能够激活静息人 NK 细胞的脱颗粒。CD16、NKG2D、NKp30、NKp44 和 NKp46 能够激活培养的 NK 细胞。NK 细胞的激活导致产生 IFN-γ 和 MIP-1β 的多功能细胞的诱导。有趣的是，只有触发 ITAM 偶联受体才能诱导多能 NK 细胞。NKp44 表现出非常敏感的反应模式，其中受体刺激的微小增加导致最大的 NK 细胞活性。相比之下，2B4 的刺激虽然为 NK 细胞黏附提供了足够的信号，但只引起很少的 NK 细胞脱颗粒。我们的数据表明，激活受体在刺激 NK 细胞方面的有效性存在差异。
