Department of Pulmonary Immunology, Center for Biomedical Research, The University of Texas Health Science Center at Tyler, Tyler, TX, United States of America.
Department of Cellular and Molecular Biology, Center for Biomedical Research, The University of Texas Health Science Center at Tyler, Tyler, TX, United States of America.
PLoS Pathog. 2020 Dec 28;16(12):e1009132. doi: 10.1371/journal.ppat.1009132. eCollection 2020 Dec.
NK cells have been shown to display adaptive traits such as memory formation akin to T and B lymphocytes. Here we show that Zika virus infection induces memory like NK cells that express CD27. Strikingly, these cells exhibit stem-like features that include expansion capacity, self-renewal pathway, differentiation into effector cells, longer telomeres and gene signature associated with hematopoietic stem cell (HSC) progenitors. This subset shared transcriptional and epigenetic changes with memory CD8 T cells, stem cells and stem like T cells. These NK cells with memory and stem cell features, which we term "NK memory stem cells", demonstrated greater antiviral potential than CD27- or naïve CD27+ NK when adoptively transferred to Zika infected mice. Our results also suggest a role for the transcription factor TCF-1 in memory and stemness features of this NK subset. This study defines a unique TCF1hi CD27+ NK subset with memory capacity and stem cell features that play a role in antiviral immunity.
自然杀伤 (NK) 细胞已被证明具有类似 T 和 B 淋巴细胞的记忆形成等适应性特征。在这里，我们表明寨卡病毒感染诱导表达 CD27 的类似记忆的 NK 细胞。引人注目的是，这些细胞表现出类似干细胞的特征，包括扩增能力、自我更新途径、分化为效应细胞、更长的端粒和与造血干细胞 (HSC) 祖细胞相关的基因特征。这个亚群与记忆 CD8 T 细胞、干细胞和类似干细胞的 T 细胞具有转录和表观遗传变化。这些具有记忆和干细胞特征的 NK 细胞，我们称之为“NK 记忆干细胞”，当被过继转移到寨卡病毒感染的小鼠中时，表现出比 CD27-或幼稚 CD27+ NK 更强的抗病毒潜力。我们的研究结果还表明转录因子 TCF-1 在这个 NK 亚群的记忆和干细胞特征中起作用。本研究定义了具有记忆能力和干细胞特征的独特 TCF1hi CD27+ NK 亚群，在抗病毒免疫中发挥作用。
