Erratum: Therapeutic Targeting of Follicular T Cells with Chimeric Antigen Receptor-Expressing Natural Killer Cells.
Erratum: Therapeutic Targeting of Follicular T Cells with Chimeric Antigen Receptor-Expressing Natural Killer Cells.
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勘误表：用表达嵌合抗原受体的自然杀伤细胞对滤泡 T 细胞进行治疗性靶向。
DOI：
10.1016/j.xcrm.2020.100080
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Waggoner,StephenN
中科院分区：
文献类型：
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作者：
Reighard,SethD;Cranert,StaceyA;Rangel,KellyM;Ali,Ayad;Gyurova,IvaylaE;delaCruz-Lynch,ArthurT;Tuazon,JasmineA;Khodoun,MaratV;Kottyan,LeahC;Smith,DavidF;Brunner,HermineI;Waggoner,StephenN
滤泡辅助性T细胞（TFH）对于疫苗和感染诱导的长期体液免疫至关重要，但过度的TFH应答可促进自身免疫和其他病理。不幸的是，没有临床干预措施存在的选择性消耗滤泡T细胞，以减轻这些疾病。我们设计了一种嵌合抗原受体（CAR），有助于特异性靶向具有高表达水平的人程序性细胞死亡蛋白1（PD-1）的细胞，这是滤泡T细胞的主要特征。表达CAR的人自然杀伤（NK）细胞在体外和狼疮样疾病的人源化小鼠模型中稳健且有区别地消除PD-1高滤泡人T细胞，同时保留B细胞和其他PD-1低T细胞亚群，包括调节性T细胞。这些结果建立了一种特异性靶向PD-1highT细胞的策略，可以作为在某些疾病状态下选择性消除致病性滤泡T细胞或其他PD-1hightarget细胞的临床工具。
Follicular helper T cells (TFH) are critical for vaccine and infection elicitation of long-lived humoral immunity, but exaggerated TFHresponses can promote autoimmunity and other pathologies. It is unfortunate that no clinical interventions exist for the selective depletion of follicular T cells to alleviate these diseases. We engineered a chimeric antigen receptor (CAR) facilitating the specific targeting of cells with high expression levels of human programmed cell death protein 1 (PD-1), a cardinal feature of follicular T cells. CAR-expressing human natural killer (NK) cells robustly and discriminately eliminated PD-1highfollicular human T cellsin vitroand in a humanized mouse model of lupus-like disease while sparing B cells and other PD-1lowT cell subsets, including regulatory T cells. These results establish a strategy for specific targeting of PD-1highT cells that can be advanced as a clinical tool for the selective depletion of pathogenic follicular T cells or other PD-1hightarget cells in certain disease states.