Department of Pathology, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA, 01605, USA.
Immunity and Pathogenesis Division, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL, 32827, USA; NanoScience Technology Center, University of Central Florida, Orlando, FL, 32826, USA.
Virology. 2020 Jan 2;539:26-37. doi: 10.1016/j.virol.2019.10.003. Epub 2019 Oct 18.
In addition to direct anti-viral activity, NK cells regulate viral pathogenesis by virtue of their cytolytic attack on activated CD4 and CD8 T cells. To gain insight into which differentiated T cell subsets are preferred NK targets, transgenic T cells were differentiated in vitro into Th0, Th1, Th2, Th17, Treg, Tc1, and Tc2 effector cells and then tested for lysis by enriched populations of lymphocytic choriomeningitis virus (LCMV)-induced activated NK cells. There was a distinct hierarchy of cytotoxicity in vitro and in vivo, with Treg, Th17, and Th2 cells being more sensitive and Th0 and Th1 cells more resistant. Some distinctions between in vitro vs in vivo generated T cells were explainable by type 1 interferon induction of class 1 histocompatibility antigens on the effector T cell subsets. NK receptor (NKR)-deficient mice and anti-NKR antibody studies identified no one essential NKR for killing, though there could be redundancies.
除了直接的抗病毒活性外，NK 细胞还通过其对激活的 CD4 和 CD8 T 细胞的细胞溶解攻击来调节病毒发病机制。为了深入了解哪些分化的 T 细胞亚群是 NK 细胞的首选靶标，体外将转基因 T 细胞分化为 Th0、Th1、Th2、Th17、Treg、Tc1 和 Tc2 效应细胞，然后用富含淋巴细胞性脉络丛脑膜炎病毒（LCMV）诱导的激活 NK 细胞的群体来测试其溶解活性。体外和体内均存在明显的细胞毒性分层，Treg、Th17 和 Th2 细胞更敏感，而 Th0 和 Th1 细胞更耐受。一些体外与体内生成的 T 细胞之间的差异可以通过 1 型干扰素诱导效应 T 细胞亚群上的 I 类主要组织相容性抗原来解释。NK 受体（NKR）缺陷小鼠和抗 NKR 抗体研究表明，不存在一种用于杀伤的必需 NKR，尽管可能存在冗余。
