Journal Article
. 2020 Oct; 218(1):.
doi: 10.1084/jem.20182232.

PD-1 restraint of regulatory T cell suppressive activity is critical for immune tolerance

Catherine L Tan 1 Juhi R Kuchroo 1 Peter T Sage 1 Dan Liang 1 Loise M Francisco 1 Jessica Buck 1 Youg Raj Thaker 1 Qianxia Zhang 2 Shannon L McArdel 1 Vikram R Juneja 1 Sun Jung Lee 1 Scott B Lovitch 1 Christine Lian 3 George F Murphy 3 Bruce R Blazar 4 Dario A A Vignali 2 Gordon J Freeman 5 Arlene H Sharpe 1 
  • PMID: 33045061
  •     70 References
  •     33 citations


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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