PD-1 Controls Follicular T Helper Cell Positioning and Function.
PD-1 Controls Follicular T Helper Cell Positioning and Function.
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PD-1 控制滤泡 T 辅助细胞的定位和功能
DOI：
10.1016/j.immuni.2018.06.012
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发表时间：
2018-08-21
期刊：
影响因子：
32.4
通讯作者：
Qi H
中科院分区：
文献类型：
--
作者：
Shi J;Hou S;Fang Q;Liu X;Liu X;Qi H
滤泡辅助性T细胞(TFH)高度表达程序性细胞死亡-1(PD-1)分子。虽然抑制T细胞受体(TCR)信号和CD28共刺激被认为是PD-1功能的主要模式，但PD-1是否以及如何调节TFH细胞的发育和功能尚不清楚。在这里，我们表明，当与组成表达PD-1配体1(PD-L1)的旁观者B细胞结合时，PD-1抑制T细胞募集到毛囊中。这种抑制包括抑制卵泡引导受体CXCR5下游的PI3K活性，这种抑制不依赖于与TCR的共同信号，并且需要ICOS信号来克服。PD-1进一步限制了TFH细胞上CXCR3的上调，使这些细胞向生发中心区聚集，在那里单个TFH和B细胞之间的PD-L1-PD-1相互作用优化了B细胞的竞争和亲和力成熟。因此，PD-1以共刺激非依赖和依赖的方式工作，控制TFH细胞的组织定位和功能。PD-1抑制滤泡T细胞募集旁观者B细胞通过ICOSL和PD-L1调节滤泡T细胞募集PD-1限制CXCR3的表达以限制Tfh细胞在GC中的定位PD-1-PD-L1相互作用增加GC亲和选择的严格性Tfh细胞高表达抑制性PD-1分子，尽管其在生发中心反应中的功能尚不清楚。Shih et al.结果表明，通过协同刺激和旁观者信号模式，PD-1抑制滤泡T细胞的募集，但促进GC区域的TfH细胞浓度，并有助于维持GC亲和力选择的严格性。
Follicular T helper (Tfh) cells highly express the programmed cell death-1 (PD-1) molecule. Whereas inhibition of T cell receptor (TCR) signaling and CD28 co-stimulation is thought to be the primary mode of PD-1 functions, whether and how PD-1 regulates Tfh cell development and function is unclear. Here we showed that, when engaged by the ensemble of bystander B cells constitutively expressing PD-1 ligand 1 (PD-L1), PD-1 inhibited T cell recruitment into the follicle. This inhibition involved suppression of PI3K activities downstream of the follicle-guidance receptor CXCR5, was independent of co-signaling with the TCR, and necessitated ICOS signaling to overcome. PD-1 further restricted CXCR3 upregulation on Tfh cells, serving to concentrate these cells toward the germinal center territory, where PD-L1-PD-1 interactions between individual Tfh and B cells optimized B cell competition and affinity maturation. Therefore, operating in both costimulation-independent and -dependent manners, PD-1 controls tissue positioning and function of Tfh cells. PD-1 suppresses follicular T cell recruitment Bystander B cells regulate follicular T cell recruitment by both ICOSL and PD-L1 PD-1 limits CXCR3 expression to confine Tfh cell localization in the GC PD-1-PD-L1 interactions increase the stringency of GC affinity selection Tfh cells highly express the inhibitory PD-1 molecule, although its function in the germinal center response is not well understood. Shi et al. show that, by operating in both costimulatory and bystander signaling mode, PD-1 suppresses follicular T cell recruitment but promotes Tfh cell concentration in the GC territory and helps maintain the stringency of GC affinity selection.
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影响因子：
4.4
作者：
Chemnitz, JM;Parry, RV;Riley, JL
通讯作者：
Riley, JL
影响因子：
32.4
作者：
Choi YS;Kageyama R;Eto D;Escobar TC;Johnston RJ;Monticelli L;Lao C;Crotty S
通讯作者：
Crotty S
影响因子：
16.6
作者：
McDonald PW;Read KA;Baker CE;Anderson AE;Powell MD;Ballesteros-Tato A;Oestreich KJ
通讯作者：
Oestreich KJ
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影响因子：
64.8
作者：
Liu, Dan;Xu, Heping;Qi, Hai
通讯作者：
Qi, Hai
影响因子：
7.3
作者：
Gibbons Johnson RM;Dong H
通讯作者：
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