PD-1/PD-L1, but not PD-1/PD-L2, interactions regulate the severity of experimental autoimmune encephalomyelitis.
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-gamma, 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.
Pubmed ID: 17182110 RIS Download
Animals | Antigens, CD274 | Antigens, CD80 | Antigens, Differentiation | Encephalomyelitis, Autoimmune, Experimental | Glycoproteins | Humans | Interferon-gamma | Interleukin-17 | Interleukin-6 | Lymph Nodes | Lymphocyte Activation | Membrane Glycoproteins | Mice | Mice, Knockout | Mice, Transgenic | Myelin-Oligodendrocyte Glycoprotein | Peptide Fragments | Peptides | Programmed Cell Death 1 Ligand 2 Protein | Programmed Cell Death 1 Receptor | Severity of Illness Index | T-Lymphocytes | Tumor Necrosis Factor-alpha