Dendritic Cell PD-L1 Limits Autoimmunity and Follicular T Cell Differentiation and Function

Abstract The programmed death (PD)-1 coinhibitory receptor regulates the balance between T cell activation and tolerance. Although the PD-1 ligands, PD-L1 and PD-L2, are expressed on a variety of cell types, the cell type–specific functions of PD-1 ligands in inducing signals through PD-1 are unknown. In this study, we use PD-L1 conditional knockout mice to investigate the cell type–specific functions of PD-L1. We demonstrate that PD-L1 expressed on dendritic cells (DCs), and to a lesser extent on B cells, attenuates the progression of experimental autoimmune encephalomyelitis and inhibits naive and effector T cells. PD-1 is highly expressed on effector populations, including T follicular helper (Tfh) cells and T follicular regulatory (Tfr) cells, which reside in germinal centers. We also show that DC PD-L1 is essential for limiting Tfh and Tfr cell differentiation. In addition, we find that PD-1 suppresses Tfh cell differentiation and help for Ig class switching, even in the presence of wild-type Tfr cells. Our work points to critical roles for PD-L1 expressed on DCs in mediating PD-1 functions.