TNF-related apoptosis-inducing ligand (TRAIL)/Apo2L suppresses experimental autoimmune encephalomyelitis in mice.
Studies have suggested that endogenous TNF-related apoptosis-inducing ligand (TRAIL)/Apo2L may suppress the induction of some autoimmune diseases in mice. Here, we show that TRAIL/Apo2L suppresses autoimmune damage in relapsing-remitting, and non-remitting models of experimental autoimmune encephalomyelitis (EAE). TRAIL/Apo2L-deficient mice and wild-type mice treated with neutralizing anti-TRAIL/Apo2L antibody displayed enhanced clinical score, increased T-cell proliferative responses to myelin oligodendrocyte glycoprotein (MOG), and increased numbers of inflammatory lesions in the spinal cord and central nervous system. TRAIL neutralization immediately before disease onset was most effective at exacerbating disease score. More importantly, therapeutic intervention with recombinant soluble TRAIL/Apo2L delayed the onset and reduced the severity of MOG-induced EAE. These data are the first to illustrate the potential therapeutic value of recombinant TRAIL/Apo2L in suppressing T-cell-mediated autoimmune diseases.
Cretney
Erika
E
Cancer Immunology Program, Sir Donald and Lady Trescowthick Laboratories, Peter MacCallum Cancer Centre, Victoria, Australia.
McQualter
Jonathan L
JL
Kayagaki
Nobuhiko
N
Yagita
Hideo
H
Bernard
Claude C A
CC
Grewal
Iqbal S
IS
Ashkenazi
Avi
A
Smyth
Mark J
MJ
D000595:Amino Acid Sequence; D000818:Animals; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000378:metabolism* / Q000517:prevention & control; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000276:immunology; D011994:Recombinant Proteins / Q000235:genetics; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*
D011994:Recombinant Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand