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

We report that PD-1 restraint of regulatory T cell suppressive activity via the PI3K-AKT pathway and metabolism is critical for immune tolerance. We generated mice that selectively lack PD-1 in Treg cells. Mice lacking PD-1 selectively in Treg cells had ameliorated experimental autoimmune encephalomyelitis (EAE) and protection from diabetes in non-obese diabetic (NOD) mice . We identified reduced signaling through the PI3K-AKT pathway as a mechanism underlying the enhanced suppressive capacity of PD-1 deficient Treg cells by undertaking bulk RNA-seq of CNS-infiltrating Treg cells. Our findings demonstrate that cell-intrinsic PD-1 restraint of Treg cells is a significant mechanism by which PD-1 inhibitory signals regulate T cell tolerance and autoimmunity. Analysis of Treg cells from mice that selctively deleted PD-1 on Treg cells compared to WT Treg cells using bulk RNA seq