title: 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-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.
authors.affiliation: Inflammation, Wyeth Research, 200 CambridgePark Dr., Cambridge, MA 02140, United States. lcarter@wyeth.com
authors.forename: Laura L
authors.initials: LL
authors.lastname: Carter
authors.forename: Michael W
authors.initials: MW
authors.lastname: Leach
authors.forename: Mihai L
authors.initials: ML
authors.lastname: Azoitei
authors.forename: Junqing
authors.initials: J
authors.lastname: Cui
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Pelker
authors.forename: Jason
authors.initials: J
authors.lastname: Jussif
authors.forename: Steve
authors.initials: S
authors.lastname: Benoit
authors.forename: Gretchen
authors.initials: G
authors.lastname: Ireland
authors.forename: Deborah
authors.initials: D
authors.lastname: Luxenberg
authors.forename: G Roger
authors.initials: GR
authors.lastname: Askew
authors.forename: Kim L
authors.initials: KL
authors.lastname: Milarski
authors.forename: Christopher
authors.initials: C
authors.lastname: Groves
authors.forename: Tom
authors.initials: T
authors.lastname: Brown
authors.forename: Brenda A
authors.initials: BA
authors.lastname: Carito
authors.forename: Karen
authors.initials: K
authors.lastname: Percival
authors.forename: Beatriz M
authors.initials: BM
authors.lastname: Carreno
authors.forename: Mary
authors.initials: M
authors.lastname: Collins
authors.forename: Suzana
authors.initials: S
authors.lastname: Marusic
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism*; D018122:B7-1 Antigen / Q000378:metabolism*; D060890:B7-H1 Antigen; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D006023:Glycoproteins / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D020381:Interleukin-17 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments / Q000276:immunology; D010455:Peptides / Q000172:deficiency / Q000378:metabolism*; D061027:Programmed Cell Death 1 Ligand 2 Protein; D061026:Programmed Cell Death 1 Receptor; D012720:Severity of Illness Index; D013601:T-Lymphocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; C498919:Cd274 protein, mouse; D006023:Glycoproteins; D020381:Interleukin-17; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D063308:Myelin-Oligodendrocyte Glycoprotein; C556977:PDCD1LG2 protein, human; C491383:Pdcd1 protein, mouse; C556978:Pdcd1lg2 protein, mouse; D010446:Peptide Fragments; D010455:Peptides; D061027:Programmed Cell Death 1 Ligand 2 Protein; D061026:Programmed Cell Death 1 Receptor; D014409:Tumor Necrosis Factor-alpha; C445081:myelin oligodendrocyte glycoprotein (35-55); D007371:Interferon-gamma