T细胞
实验性自身免疫性脑脊髓炎
自身免疫
细胞生物学
免疫系统
免疫耐受
ZAP70型
调节性T细胞
PI3K/AKT/mTOR通路
生物
FOXP3型
克隆无能
免疫学
白细胞介素2受体
抗原
化学
细胞毒性T细胞
过继性细胞移植
CD8型
周边公差
信号转导
体外
生物化学
作者
Catherine L. Tan,Juhi R. Kuchroo,Peter T. Sage,Dan Liang,Loise M. Francisco,Jessica Buck,Youg Raj Thaker,Qianxia Zhang,Shannon L. McArdel,Vikram R. Juneja,Sun Sook Lee,Scott B. Lovitch,Arash Mostaghimi,George F. Murphy,Bruce R. Blazar,Dario A. A. Vignali,Gordon J. Freeman,Arlene H. Sharpe
摘要
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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