title: Mechanisms of neonatal tolerance induced in an animal model for primary Sjögren's syndrome by intravenous administration of autoantigen.
abstract: Neonatal exposure to autoantigen is believed to induce effective antigen-specific T-cell tolerance in experimental models of autoimmunity. We have identified 120 kDa alpha-fodrin autoantigen in an animal model for primary Sjögren's syndrome (SS), that has been determined as a candidate autoantigen in both an animal model and the patients with primary SS. We demonstrate here that neonatal injection of autoantigen induce relevant tolerance when treated with intravenous (i.v.) administration within 24 h after birth, but not with i.v. injection after the thymectomy or with intraperitoneal injection. Autoantigen-specific T-cell response was significantly reduced in mice induced neonatal tolerance, and the activation markers of splenic CD4+ T cells were down-regulated in mice treated with neonatal administration. Because we detected that neonatal i.v. injection of autoantigen prevented Th1 response, it is possible that the autoantigen administration within 24 h after birth induce regulatory T cells that had a protective effect against Th1-mediated autoimmune diseases. These results indicate that the prevention of the spontaneous anti-120 kDa alpha-fodrin response in vivo, by tolerization of the autoantigen-reactive T cells, blocked the development of autoimmune lesions in an animal model for primary SS.
authors.affiliation: Department of Pathology, Tokushima University School of Dentistry, 3 Kuramotocho, Tokushima 770, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Saegusa
authors.forename: N
authors.initials: N
authors.lastname: Ishimaru
authors.forename: N
authors.initials: N
authors.lastname: Haneji
authors.forename: K
authors.initials: K
authors.lastname: Yanagi
authors.forename: T
authors.initials: T
authors.lastname: Yoneda
authors.forename: I
authors.initials: I
authors.lastname: Saito
authors.forename: Y
authors.initials: Y
authors.lastname: Hayashi
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000276:immunology*; D015703:Antigens, CD / Q000096:biosynthesis; D001324:Autoantigens / Q000008:administration & dosage / Q000276:immunology / Q000633:toxicity*; D001327:Autoimmune Diseases / Q000209:etiology / Q000276:immunology*; D002352:Carrier Proteins / Q000008:administration & dosage / Q000276:immunology / Q000633:toxicity*; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D005260:Female; D007108:Immune Tolerance / Q000276:immunology*; D007275:Injections, Intravenous; D008213:Lymphocyte Activation; D051379:Mice; D008817:Mice, Mutant Strains; D008840:Microfilament Proteins / Q000008:administration & dosage / Q000276:immunology / Q000633:toxicity*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology / Q000633:toxicity; D012859:Sjogren's Syndrome / Q000209:etiology / Q000276:immunology*; D013047:Specific Pathogen-Free Organisms; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D013934:Thymectomy; D013049:Spectrin
chemical_list: D015703:Antigens, CD; D001324:Autoantigens; D002352:Carrier Proteins; D016207:Cytokines; D008840:Microfilament Proteins; D011994:Recombinant Proteins; D013049:Spectrin