PD-1/PD-L1, but not PD-1/PD-L2, interactions regulate the severity of experimental autoimmune encephalomyelitis.

Abstract Interactions between PD-1 and its two differentially expressed ligands, PD-L1 and PD-L2, attenuate T cell activation and effector function. To determine the role of these molecules in autoimmune disease of the CNS, PD-1−/−, PD-L1−/− and PD-L2−/− mice were generated and immunized to induce experimental autoimmune encephalomyelitis (EAE). PD-1−/− and PD-L1−/− mice developed more severe EAE than wild type and PD-L2−/− mice. Consistent with this, PD-1−/− and PD-L1−/− cells produced elevated levels of the pro-inflammatory cytokines IFN-γ, TNF, IL-6 and IL-17. These results demonstrate that interactions between PD-1/PD-L1, but not PD-1/PDL-2, are crucial in attenuating T cell responses in EAE.