title: Lymphotoxin beta receptor-Ig fusion protein treatment blocks actively induced, but not adoptively transferred, uveitis in Lewis rats.
abstract: Previous studies have shown that treatment of rodents with a lymphotoxin (LT) beta receptor-Ig fusion protein (LTbetaR-Ig), which binds to both LT and LIGHT, prevents the development of autoimmune diseases, but the mechanism involved is unclear. To explore the potential role of LT or LIGHT in the pathogenesis of autoimmune uveitis, uveitis was induced in Lewis rats either by immunization with an uveitogenic peptide, R16, derived from the interphotoreceptor retinoid-binding protein, or by adoptive transfer of R16-specific T cells. Interestingly, LTbetaR-Ig treatment completely prevented actively induced uveitis, but not the adoptively transferred disease. We also show that LTbetaR-Ig-treated R16-injected rats had a significantly decreased T cell response to R16 and that herpesvirus entry mediator (HVEM)-Ig, a fusion protein that blocks LIGHT, also inhibited disease development. Our results suggest that LT or LIGHT plays a critical role in the induction, rather than the effector, phase of the disease.
authors.affiliation: Department of Ophthalmology and Visual Sciences, Kentucky Lions Eye Center, University of Louisville, 40202, USA. h0sha01@louisville.edu
authors.forename: Hui
authors.initials: H
authors.lastname: Shao
authors.forename: Yangxin
authors.initials: Y
authors.lastname: Fu
authors.forename: Lei
authors.initials: L
authors.lastname: Song
authors.forename: Sheher
authors.initials: S
authors.lastname: Sun
authors.forename: Herry J
authors.initials: HJ
authors.lastname: Kaplan
authors.forename: Deming
authors.initials: D
authors.lastname: Sun
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000276:immunology / Q000517:prevention & control*; D005260:Female; D018796:Immunoconjugates / Q000494:pharmacology / Q000627:therapeutic use*; D053259:Lymphotoxin beta Receptor; D008233:Lymphotoxin-alpha / Q000502:physiology*; D008565:Membrane Proteins / Q000502:physiology*; D010446:Peptide Fragments / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000627:therapeutic use*; D053240:Receptors, Tumor Necrosis Factor, Member 14; D011991:Receptors, Virus / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D012177:Retinol-Binding Proteins / Q000276:immunology; D013047:Specific Pathogen-Free Organisms; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D014605:Uveitis / Q000188:drug therapy / Q000276:immunology / Q000517:prevention & control*; D014611:Vaccination
chemical_list: D001324:Autoantigens; D018796:Immunoconjugates; D053259:Lymphotoxin beta Receptor; D008233:Lymphotoxin-alpha; D008565:Membrane Proteins; D010446:Peptide Fragments; D018124:Receptors, Tumor Necrosis Factor; D053240:Receptors, Tumor Necrosis Factor, Member 14; D011991:Receptors, Virus; D011993:Recombinant Fusion Proteins; D012177:Retinol-Binding Proteins; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14; D014409:Tumor Necrosis Factor-alpha; C084432:immunodominant R16 protein, rat