title: Amelioration of experimental autoimmune uveoretinitis by pretreatment with a pathogenic peptide in liposome and anti-CD40 ligand monoclonal antibody.
abstract: We have defined a peptide K2 (ADKDVVVLTSSRTGGV) that corresponds to residues 201-216 of bovine interphotoreceptor retinoid-binding protein and induces experimental autoimmune uveoretinitis (EAU)4 in H-2Ak-carrying mice (H-2Ak mice). In this study, we attempted to ameliorate EAU in the H-2Ak mice without nonspecific suppression of T cell responses. Preceding s.c. administration of liposomes including K2 (liposomal K2) specifically inhibited subsequent generation of T cell response to K2. The same result was obtained with a combination of OVA323-339 peptide and the OVA-specific TCR-transgenic T cells. It was suggested that the inhibition was mainly attributed to peripheral anergy induction of T cells specific for the peptide Ag, although specific cell death might also be involved in the inhibition. Pretreatment with liposomal K2 also considerably abolished IFN-gamma production but not IL-4 production. The specific inhibitory effect of the pretreatment with liposomal peptide was augmented by a simultaneous administration of anti-CD40 ligand (anti-CD40L) mAb. Moreover, it was shown that the pretreatment with liposomal K2 reduced both the incidence and severity of the subsequent K2-induced EAU, and the simultaneous administration of anti-CD40L mAb augmented this preventive effect by liposomal K2. Our findings demonstrate that the s.c. administration of liposomal pathogenic peptide and anti-CD40L mAb can be applied to preventing autoimmune diseases without detrimental nonspecific suppression of T cell responses.
authors.affiliation: Division of Immunobiology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Namba
authors.forename: K
authors.initials: K
authors.lastname: Ogasawara
authors.forename: N
authors.initials: N
authors.lastname: Kitaichi
authors.forename: T
authors.initials: T
authors.lastname: Morohashi
authors.forename: Y
authors.initials: Y
authors.lastname: Sasamoto
authors.forename: S
authors.initials: S
authors.lastname: Kotake
authors.forename: H
authors.initials: H
authors.lastname: Matsuda
authors.forename: K
authors.initials: K
authors.lastname: Iwabuchi
authors.forename: C
authors.initials: C
authors.lastname: Iwabuchi
authors.forename: S
authors.initials: S
authors.lastname: Ohno
authors.forename: K
authors.initials: K
authors.lastname: Onoé
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D001327:Autoimmune Diseases / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D019013:CD40 Antigens / Q000378:metabolism; D023201:CD40 Ligand; D002417:Cattle; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D004337:Drug Carriers; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005136:Eye Proteins; D005260:Female; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D007279:Injections, Subcutaneous; D008024:Ligands; D008081:Liposomes; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000008:administration & dosage*; D012173:Retinitis / Q000209:etiology / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D012177:Retinol-Binding Proteins / Q000008:administration & dosage; D013601:T-Lymphocytes / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D014605:Uveitis / Q000209:etiology / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D000099214:Retinol-Binding Proteins, Interstitial
chemical_list: D000911:Antibodies, Monoclonal; D019013:CD40 Antigens; D023201:CD40 Ligand; D016207:Cytokines; D004337:Drug Carriers; D018984:Epitopes, T-Lymphocyte; D005136:Eye Proteins; D007166:Immunosuppressive Agents; D008024:Ligands; D008081:Liposomes; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D012177:Retinol-Binding Proteins; D000099214:Retinol-Binding Proteins, Interstitial