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.
PD-1 restraint of regulatory T cell suppressive activity is critical for immune tolerance
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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 Jung Lee, Scott B. Lovitch, Christine Lian, George F. Murphy, Bruce R. Blazar, Dario A.A. Vignali, Gordon J. Freeman, Arlene H. Sharpe; PD-1 restraint of regulatory T cell suppressive activity is critical for immune tolerance. J Exp Med 4 January 2021; 218 (1): e20182232. doi: https://doi.org/10.1084/jem.20182232
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