PD-1 restraint of regulatory T cell suppressive activity is critical for immune tolerance.
PD-1 restraint of regulatory T cell suppressive activity is critical for immune tolerance.
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PD-1抑制调节性T细胞抑制活性对免疫耐受至关重要。
DOI：
10.1084/jem.20182232
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发表时间：
2021-01-04
期刊：
影响因子：
--
通讯作者：
Sharpe AH
中科院分区：
文献类型：
--
作者：
Tan CL;Kuchroo JR;Sage PT;Liang D;Francisco LM;Buck J;Thaker YR;Zhang Q;McArdel SL;Juneja VR;Lee SJ;Lovitch SB;Lian C;Murphy GF;Blazar BR;Vignali DAA;Freeman GJ;Sharpe AH
Tan等人为理解PD-1如何调节调节性T （T reg）细胞提供了新的见解。更具体地说，本研究表明，在体外和体内，T reg细胞上PD-1的缺失导致T reg细胞抑制功能增强。这些发现对于理解PD-1和pd - l1介导的检查点阻断的疗效具有临床意义。通过PD-1通路的抑制信号调节T细胞活化、T细胞耐受和T细胞衰竭。PD-1功能的研究主要集中在效应T细胞上。关于PD-1在调节性T细胞（T reg）中的功能，我们所知甚少。为了研究PD-1在T细胞中的作用，我们制造了T细胞中选择性缺乏PD-1的小鼠。pd -1缺陷T细胞表现出活化的表型和增强的免疫抑制功能。通过改善实验性自身免疫性脑脊髓炎（EAE）和在T细胞中选择性缺乏PD-1的非肥胖糖尿病（NOD）小鼠中对糖尿病的保护，证明了PD-1缺陷T细胞有效抑制能力的体内意义。我们发现通过PI3K-AKT通路的信号传导减少是pd -1缺陷T细胞抑制能力增强的机制。我们的研究结果表明，细胞内PD-1抑制T细胞是PD-1抑制信号调节T细胞耐受性和自身免疫的重要机制。
Tan et al. provide novel insights into understanding how PD-1 regulates regulatory T (T reg) cells. More specifically, this study demonstrates that loss of PD-1 on T reg cells leads to enhanced T reg cell suppressor function in vitro and in vivo. These findings have clinical relevance for understanding the efficacy of PD-1– and PD-L1–mediated checkpoint blockade. Inhibitory signals through the PD-1 pathway regulate T cell activation, T cell tolerance, and T cell exhaustion. Studies of PD-1 function have focused primarily on effector T cells. Far less is known about PD-1 function in regulatory T (T reg) cells. To study the role of PD-1 in T reg cells, we generated mice that selectively lack PD-1 in T reg cells. PD-1–deficient T reg cells exhibit an activated phenotype and enhanced immunosuppressive function. The in vivo significance of the potent suppressive capacity of PD-1–deficient T reg cells is illustrated by ameliorated experimental autoimmune encephalomyelitis (EAE) and protection from diabetes in nonobese diabetic (NOD) mice lacking PD-1 selectively in T reg cells. We identified reduced signaling through the PI3K–AKT pathway as a mechanism underlying the enhanced suppressive capacity of PD-1–deficient T reg cells. Our findings demonstrate that cell-intrinsic PD-1 restraint of T reg cells is a significant mechanism by which PD-1 inhibitory signals regulate T cell tolerance and autoimmunity.
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DOI：
10.1084/jem.20160801
发表时间：
2017-04-03
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Juneja VR;McGuire KA;Manguso RT;LaFleur MW;Collins N;Haining WN;Freeman GJ;Sharpe AH
通讯作者：
Sharpe AH
影响因子：
17.1
作者：
Amarnath S;Mangus CW;Wang JC;Wei F;He A;Kapoor V;Foley JE;Massey PR;Felizardo TC;Riley JL;Levine BL;June CH;Medin JA;Fowler DH
通讯作者：
Fowler DH
影响因子：
4
作者：
Franckaert, Dean;Dooley, James;Roos, Evelyne;Floess, Stefan;Huehn, Jochen;Luche, Herve;Fehling, Hans Joerg;Liston, Adrian;Linterman, Michelle A.;Schlenner, Susan M.
通讯作者：
Schlenner, Susan M.
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
影响因子：
29.7
作者：
Josefowicz SZ;Lu LF;Rudensky AY
通讯作者：
Rudensky AY