Role for early-differentiated natural killer cells in infectious mononucleosis
Role for early-differentiated natural killer cells in infectious mononucleosis
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DOI：
10.1182/blood-2014-01-553024
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发表时间：
2014-10-16
期刊：
影响因子：
20.3
通讯作者：
Nadal, David
中科院分区：
文献类型：
--
作者：
Azzi, Tarik;Luenemann, Anna;Nadal, David
越来越多的证据表明，人类自然杀伤(NK)细胞的表型和功能是不同的，并由几个分化阶段组成。此外，NK细胞亚群已被证明在实验小鼠感染疱疹病毒期间表现出适应性免疫特征，并在人类病毒感染期间优先扩张。然而，NK细胞在急性症状性EB病毒(EBV)感染，即传染性单核细胞增多症(IM)中的表型和作用尚不清楚。在这里，我们纵向评估了儿童IM患者NK细胞亚群的动力学、分化和增殖。结果表明，急性IM以早期分化的CD56(DIM)NKG2A(+)免疫球蛋白样受体NK细胞优先增殖为特征。此外，这种NK细胞亚群表现出终末分化的特征，并在急性IM后至少前6个月内以较高的频率持续存在。最后，我们证明这个NK细胞亚群在暴露于表达裂解抗原的EB病毒感染的B细胞时优先脱颗粒和增殖。因此，早期分化的NK细胞可能在初次感染这种持续的肿瘤相关病毒的免疫控制中发挥关键作用。
A growing body of evidence suggests that the human natural killer (NK)-cell compartment is phenotypically and functionally heterogeneous and is composed of several differentiation stages. Moreover, NK-cell subsets have been shown to exhibit adaptive immune features during herpes virus infection in experimental mice and to expand preferentially during viral infections in humans. However, both phenotype and role of NK cells during acute symptomatic Epstein-Barr virus (EBV) infection, termed infectious mononucleosis (IM), remain unclear. Here, we longitudinally assessed the kinetics, the differentiation, and the proliferation of subsets of NK cells in pediatric IM patients. Our results indicate that acute IM is characterized by the preferential proliferation of early-differentiated CD56(dim) NKG2A(+) immunoglobulin-like receptor NK cells. Moreover, this NK-cell subset exhibits features of terminal differentiation and persists at higher frequency during at least the first 6 months after acute IM. Finally, we demonstrate that this NK-cell subset preferentially degranulates and proliferates on exposure to EBV-infected B cells expressing lytic antigens. Thus, early-differentiated NK cells might play a key role in the immune control of primary infection with this persistent tumor-associated virus.