Generation of cellular immune memory and B-cell immunity is impaired by natural killer cells.
Generation of cellular immune memory and B-cell immunity is impaired by natural killer cells.
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DOI：
10.1038/ncomms7375
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发表时间：
2015-02-27
影响因子：
16.6
通讯作者：
Waggoner, Stephen N.
中科院分区：
文献类型：
--
作者：
Rydyznski, Carolyn;Daniels, Keith A.;Karmele, Erik P.;Brooks, Taylor R.;Mahl, Sarah E.;Moran, Michael T.;Li, Caimei;Sutiwisesak, Rujapak;Welsh, Raymond M.;Waggoner, Stephen N.
大多数疫苗的目标是诱导能够保护宿主免受细胞毒性机制、细胞因子和高亲和力抗体感染的长期记忆T细胞和B细胞。然而，开发针对艾滋病毒和丙型肝炎病毒等主要人类病原体的疫苗的努力尚未取得成功，因此强调需要新的方法来绕过限制保护性免疫诱导的免疫调节机制。在这里，我们表明小鼠自然杀伤（NK）细胞在急性感染后抑制长寿命的病毒特异性记忆T细胞和b细胞的产生以及病毒特异性抗体的产生。在机制上，NK细胞在感染的最初几天以穿孔依赖的方式抑制CD4 T细胞和滤泡辅助性T细胞（TFH），导致生发中心（GC）反应减弱和免疫记忆减弱。我们预计，缓解NK细胞介导的免疫抑制的创新策略应该有助于开发针对难以预防的感染的有效新疫苗。
The goal of most vaccines is the induction of long-lived memory T and B cells capable of protecting the host from infection by cytotoxic mechanisms, cytokines and high-affinity antibodies. However, efforts to develop vaccines against major human pathogens like HIV and HCV have not been successful, thereby highlighting the need for novel approaches to circumvent immunoregulatory mechanisms that limit induction of protective immunity. Here we show that mouse natural killer (NK) cells inhibit generation of long-lived virus-specific memory T- and B-cells as well as virus-specific antibody production after acute infection. Mechanistically, NK cells suppressed CD4 T cells and follicular helper T cells (TFH) in a perforin-dependent manner during the first few days of infection, resulting in a weaker germinal center (GC) response and diminished immune memory. We anticipate that innovative strategies to relieve NK cell-mediated suppression of immunity should facilitate development of efficacious new vaccines targeting difficult-to-prevent infections.
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影响因子：
30.5
作者：
Kaech, SM;Tan, JT;Ahmed, R
通讯作者：
Ahmed, R
影响因子：
64.8
作者：
KAGI, D;LEDERMANN, B;HENGARTNER, H
通讯作者：
HENGARTNER, H
影响因子：
30.5
作者：
Kelly, JM;Darcy, PK;Smyth, MJ
通讯作者：
Smyth, MJ
2B4 作为小鼠自然杀伤细胞上的非主要组织相容性复合物结合抑制受体。
DOI：
10.1084/jem.20031989
发表时间：
2004-05-03
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Lee KM;McNerney ME;Stepp SE;Mathew PA;Schatzle JD;Bennett M;Kumar V
通讯作者：
Kumar V
影响因子：
64.8
作者：
Dong, C;Juedes, AE;Flavell, RA
通讯作者：
Flavell, RA