Study of experimental autoimmune uveoretinitis

1992 Fiscal Year Final Research Report Summary

• Project/Area Number: 03670187
• Research Category: Grant-in-Aid for General Scientific Research (C)
• Allocation Type: Single-year Grants
• Research Field: Experimental pathology
• Research Institution: Aichi Cancer Center
• Principal Investigator: TAGUCHI Osamu Aichi Cancer Center Research Institute, Laboratory of Experimental Pathology, Senior Researcher, 研究所・病理学第2部, 主任研究員 (00142167)
• Project Period (FY): 1991 – 1992
• Keywords: uveoretinitis / nude mouse / autoimmune disease / thymic chimera / IRBP / thymus

Research Abstract

This paper describes the spontaneous occurrence of an autoimmune uveoretinitis in nude (nu/nu) mice reconstituted when 4 weeks old by the grafting of rat embryonic thymus (TG nude). The uveoretinitis was characterized histologically by progressive loss of the photoreceptor layer, observed in 4.0, 17.6, 42.9 and 71.4 percent of such mice at 3, 5, 7 and 12 months of age, respectively. Mice with uveoretinitis were shown to have serum IgG antibody reactive by indirect immunofluorescence with retinal photoreceptors, and with interphotoreceptor retinoid-binding protein (IRBP), but not retinal S-antigen, by immunoblotting and ELISA. IRBP is an approximately 140 kDa glycoprotein consisting of about 1260 amino acid residues. We found that residues 1182-1194 is the immunodominant determinant in TG nude mice, and that tryptophan at residue 1182 and proline at residue 1194 are agretopes of the peptide. A uveoretinitis could be adoptively transferred to syngeneic ungrafted nude mice by splenic CD4-positive T cells from diseased animals. This is the first experimental model of a (T-cell mediated) autoimmune uveoretinitis which develops spontaneously and which is not dependent upon deliberate sensitization with retinal antigens and adjuvants.

Research Products

• [Publications] ICHIKAWA,T.et.al.: "Spontaneous development of autoimmune uveoretinitis in nude mice following reconstitution with embryonic rat thymus" Clin.Exp.Immunol.86. 112-117 (1991)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] INOUE,H.et.al.: "Identification of highly immunopathogenic peptides in bovine IRBP" 3rd Int.Symp.on Uveitis.
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] TAKAHASHI,T.et.al.: "Effects of IRBP immunization with incomplete Freund's adjuvant on autoimmune uveoretinitis-prone mice" 3rd Int.Symp.on Uveitis.
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] TAKEUCHI,M.et.al.: "Murine T cell response to synthetic peptides derived from immunodominant determinants of IRBP" 3rd Int.Symp.on Uveitis.
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Ichikawa,T., Taguchi,O., Takahashi,T., Ikeda,H., Takeuchi,M., Tanaka,T., Usui,M. & Nishizuka,Y.: "Spontaneous development of autoimmune uveoretinitis in nude mice following reconstitution with embryonic rat thymus" Clin. Exp. Immunol. 86. 112-117 (1991)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Inoue,H., Tanaka,T., Fujita,K., Uehara,R. Ando,S. & Taguchi,O.: "Identification of highly immuno- pathogenic peptides in bovine IRBP" 3rd Int. Symp. on Uveitis.
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Takahashi,T., Taguchi,O. & Usui,M.: "Effects of IRBP immunization with incomplete Freund's adjuvant on autoimmune uveoretinitis-prone mice" 3rd Int. Symp. on Uveitis.
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Takeuchi,M., Taguchi,O., Inoue,H., Takahachi,T., Sakai,J. & Usui,M.: "Murine T cell response to synthetic peptides derived from immunodominant determinants of IRBP" 3rd Int. Symp. on Uveitis.
  • Description: 「研究成果報告書概要(欧文)」より