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.
Carter
Laura L
LL
Inflammation, Wyeth Research, 200 CambridgePark Dr., Cambridge, MA 02140, United States. lcarter@wyeth.com
Leach
Michael W
MW
Azoitei
Mihai L
ML
Cui
Junqing
J
Pelker
Jeffrey W
JW
Jussif
Jason
J
Benoit
Steve
S
Ireland
Gretchen
G
Luxenberg
Deborah
D
Askew
G Roger
GR
Milarski
Kim L
KL
Groves
Christopher
C
Brown
Tom
T
Carito
Brenda A
BA
Percival
Karen
K
Carreno
Beatriz M
BM
Collins
Mary
M
Marusic
Suzana
S
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
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