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

Laura L Carter; Michael W Leach; Mihai L Azoitei; Junqing Cui; Jeffrey W Pelker; Jason Jussif; Steve Benoit; Gretchen Ireland; Deborah Luxenberg; G Roger Askew; Kim L Milarski; Christopher Groves; Tom Brown; Brenda A Carito; Karen Percival; Beatriz M Carreno; Mary Collins; Suzana Marusic

doi:10.1016/j.jneuroim.2006.10.006

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

J Neuroimmunol. 2007 Jan;182(1-2):124-34. doi: 10.1016/j.jneuroim.2006.10.006. Epub 2006 Dec 19.

Authors

Laura L Carter¹, Michael W Leach, Mihai L Azoitei, Junqing Cui, Jeffrey W Pelker, Jason Jussif, Steve Benoit, Gretchen Ireland, Deborah Luxenberg, G Roger Askew, Kim L Milarski, Christopher Groves, Tom Brown, Brenda A Carito, Karen Percival, Beatriz M Carreno, Mary Collins, Suzana Marusic

Affiliation

¹ Inflammation, Wyeth Research, 200 CambridgePark Dr., Cambridge, MA 02140, United States. lcarter@wyeth.com

PMID: 17182110
DOI: 10.1016/j.jneuroim.2006.10.006

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.

MeSH terms

Animals
Antigens, Differentiation / metabolism*
B7-1 Antigen / metabolism*
B7-H1 Antigen
Encephalomyelitis, Autoimmune, Experimental / immunology
Encephalomyelitis, Autoimmune, Experimental / metabolism
Encephalomyelitis, Autoimmune, Experimental / pathology
Encephalomyelitis, Autoimmune, Experimental / physiopathology*
Glycoproteins / immunology
Humans
Interferon-gamma / biosynthesis
Interleukin-17 / biosynthesis
Interleukin-6 / biosynthesis
Lymph Nodes / metabolism
Lymph Nodes / pathology
Lymphocyte Activation
Membrane Glycoproteins / deficiency
Membrane Glycoproteins / metabolism*
Mice
Mice, Knockout
Mice, Transgenic
Myelin-Oligodendrocyte Glycoprotein
Peptide Fragments / immunology
Peptides / deficiency
Peptides / metabolism*
Programmed Cell Death 1 Ligand 2 Protein
Programmed Cell Death 1 Receptor
Severity of Illness Index
T-Lymphocytes / immunology
Tumor Necrosis Factor-alpha / biosynthesis

Substances

Antigens, Differentiation
B7-1 Antigen
B7-H1 Antigen
Cd274 protein, mouse
Glycoproteins
Interleukin-17
Interleukin-6
Membrane Glycoproteins
Myelin-Oligodendrocyte Glycoprotein
PDCD1LG2 protein, human
Pdcd1 protein, mouse
Pdcd1lg2 protein, mouse
Peptide Fragments
Peptides
Programmed Cell Death 1 Ligand 2 Protein
Programmed Cell Death 1 Receptor
Tumor Necrosis Factor-alpha
myelin oligodendrocyte glycoprotein (35-55)
Interferon-gamma