PD-1 regulates extrathymic regulatory T-cell differentiation.
PD-1 regulates extrathymic regulatory T-cell differentiation.
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DOI：
10.1002/eji.201344423
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发表时间：
2014-09
影响因子：
5.4
通讯作者：
Kline, Justin
中科院分区：
文献类型：
--
作者：
Chen, Xiufen;Fosco, Dominick;Kline, Douglas E.;Meng, Liping;Nishi, Saki;Savage, Peter A.;Kline, Justin
调节性T细胞（Treg）和程序性死亡-1/程序性死亡配体-1 （PD-1/PD-L1）通路都是维持外周对自身抗原耐受的关键。一个重要的Treg细胞亚群组成性地表达PD-1，这促使人们研究PD-1/PD-L1相互作用在体内Treg细胞发育、功能和诱导中的作用。在pd -1缺陷小鼠中，Treg细胞的表型和丰度没有显著改变。多克隆和单特异性Treg细胞的胸腺发育不受PD-1缺乏的负面影响。在体内和体外，PD-1−/−Treg细胞的抑制功能与PD-1+/+细胞相似。然而，在三种不同的体内实验环境中，PD-1−/−常规CD4+ T细胞向外周诱导Treg （pTreg）细胞分化的趋势明显减弱。我们的研究结果表明，PD-1对于胸腺（tTreg） treg细胞的发育和抑制功能是必不可少的，但对于体内pTreg细胞的胸腺外分化至关重要。这些数据表明，抗体阻断PD-1/PD-L1通路可能通过直接作用于传统T细胞和抑制pTreg细胞的分化来增强T细胞反应。
Regulatory T (Treg) cells and the programmed death-1/programmed death ligand-1 (PD-1/PD-L1) pathway are both critical for maintaining peripheral tolerance to self antigens. A significant subset of Treg cells constitutively expresses PD-1, which prompted an investigation into the role of PD-1/PD-L1 interactions in Treg-cell development, function and induction in vivo. The phenotype and abundance of Treg cells was not significantly altered in PD-1-deficient mice. The thymic development of polyclonal and monospecific Treg cells was not negatively impacted by PD-1 deficiency. The suppressive function of PD-1−/− Treg cells was similar to their PD-1+/+ counterparts both in vitro and in vivo. However, in three different in vivo experimental settings, PD-1−/− conventional CD4+ T cells demonstrated a strikingly diminished tendency toward differentiation into peripherally induced Treg (pTreg) cells. Our results demonstrate that PD-1 is dispensable for thymic (tTreg) Treg-cell development and suppressive function, but is critical for the extrathymic differentiation of pTreg cells in vivo. These data suggest that antibody blockade of the PD-1/PD-L1 pathway may augment T-cell responses by acting directly on conventional T cells, and also by suppressing the differentiation of pTreg cells.
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影响因子：
32.4
作者：
Fontenot, JD;Rasmussen, JP;Rudensky, AY
通讯作者：
Rudensky, AY
影响因子：
3.7
作者：
Akimova T;Beier UH;Wang L;Levine MH;Hancock WW
通讯作者：
Hancock WW
影响因子：
32.4
作者：
Guo, Xiaohuan;Qiu, Ju;Tu, Tony;Yang, Xuanming;Deng, Liufu;Anders, Robert A.;Zhou, Liang;Fu, Yang-Xin
通讯作者：
Fu, Yang-Xin
影响因子：
32.4
作者：
Haribhai D;Williams JB;Jia S;Nickerson D;Schmitt EG;Edwards B;Ziegelbauer J;Yassai M;Li SH;Relland LM;Wise PM;Chen A;Zheng YQ;Simpson PM;Gorski J;Salzman NH;Hessner MJ;Chatila TA;Williams CB
通讯作者：
Williams CB
DOI：
10.1084/jem.20090847
发表时间：
2009-12-21
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Francisco LM;Salinas VH;Brown KE;Vanguri VK;Freeman GJ;Kuchroo VK;Sharpe AH
通讯作者：
Sharpe AH