title: TNF-related apoptosis-inducing ligand (TRAIL)/Apo2L suppresses experimental autoimmune encephalomyelitis in mice.
abstract: 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.
authors.affiliation: Cancer Immunology Program, Sir Donald and Lady Trescowthick Laboratories, Peter MacCallum Cancer Centre, Victoria, Australia.
authors.forename: Erika
authors.initials: E
authors.lastname: Cretney
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: McQualter
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Kayagaki
authors.forename: Hideo
authors.initials: H
authors.lastname: Yagita
authors.forename: Claude C A
authors.initials: CC
authors.lastname: Bernard
authors.forename: Iqbal S
authors.initials: IS
authors.lastname: Grewal
authors.forename: Avi
authors.initials: A
authors.lastname: Ashkenazi
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Smyth
mesh_terms: 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*
chemical_list: D011994:Recombinant Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand