Abstract
Disease progression in experimental autoimmune encephalomyelitis (EAE) is regulated by programmed death receptor 1 (PD‐1) and its ligands, B7‐H1 (programmed death ligand 1 (PD‐L1)) and B7‐DC (PD‐L2). B7‐H1 and B7‐DC have negative regulatory effects upon binding PD‐1 on activated T cells and B7‐H1 deficiency increases severity of both diabetes and EAE. However, the role of PD‐L expression on different APC in the CNS in regulating local T‐cell function during relapsing EAE has not been examined. Our data show that the majority of CNS CD4^+^ T cells isolated during acute EAE are PD‐1^+^, and T cells specific for relapse‐associated epitopes express PD‐1 upon antigen stimulation in the CNS. B7‐H1 and B7‐DC are differentially expressed on discrete APC populations in the inflamed CNS. B7‐H1 and PD‐1 have mainly inhibitory functions on CNS T cells. B7‐H1 negatively regulates the stimulation of activated PD‐1^+^ T~H~ cells, in co‐cultures with microglia and different CNS‐infiltrating APC presenting endogenously processed peptides. The preponderance of IFN‐γ^+^ versus IL‐17^+^ T cells in the CNS of B7‐H1^−/−^ mice suggests that B7‐H1 more selectively suppresses T~H~‐1 than T~H~‐17 responses in vivo. In contrast, blockade of B7‐DC has less pronounced regulatory effects. Overall, the results demonstrate that B7‐H1 expressed by CNS myeloid APC negatively regulates T‐cell activation during acute relapsing EAE.