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

• DOI: 10.1084/jem.20182232
• Publication Date: 2020-10-13T18:44:33Z
• Authors: 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
• Keywords: Peripheral tolerance; ZAP70; Regulatory T cell; NOD mice

Inhibitory signals through the PD-1 pathway regulate T cell activation, tolerance, and exhaustion. Studies of function have focused primarily on effector cells. Far less is known about in regulatory (T reg) To study role reg cells, we generated mice that selectively lack PD-1–deficient cells exhibit an activated phenotype enhanced immunosuppressive function. The vivo significance potent suppressive capacity illustrated by ameliorated experimental autoimmune encephalomyelitis (EAE) protection from diabetes nonobese diabetic (NOD) lacking We identified reduced signaling PI3K–AKT as a mechanism underlying Our findings demonstrate cell-intrinsic restraint significant which inhibitory tolerance autoimmunity.