| First Author | Tan CL | Year | 2021 |
| Journal | J Exp Med | Volume | 218 |
| Issue | 1 | PubMed ID | 33045061 |
| Mgi Jnum | J:307777 | Mgi Id | MGI:6509791 |
| Doi | 10.1084/jem.20182232 | Citation | Tan CL, et al. (2021) PD-1 restraint of regulatory T cell suppressive activity is critical for immune tolerance. J Exp Med 218(1) |
| abstractText | 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. |
