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. 1991 Oct;86(1):112–117. doi: 10.1111/j.1365-2249.1991.tb05782.x

Spontaneous development of autoimmune uveoretinitis in nude mice following reconstitution with embryonic rat thymus.

T Ichikawa 1, O Taguchi 1, T Takahashi 1, H Ikeda 1, M Takeuchi 1, T Tanaka 1, M Usui 1, Y Nishizuka 1
PMCID: PMC1554149  PMID: 1914224

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. The uveoretinitis was characterized histologically by progressive loss of the photoreceptor layer, observed in 4.0, 17.6, 42.9% and 71.4% 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. A uveoretinitis could be adoptively transferred to syngeneic ungrafted nude mice by splenic CD4+ 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.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Broekhuyse R. M., Winkens H. J., Kuhlmann E. D. Induction of experimental autoimmune uveoretinitis and pinealitis by IRBP. Comparison to uveoretinitis induced by S-antigen and opsin. Curr Eye Res. 1986 Mar;5(3):231–240. doi: 10.3109/02713688609020048. [DOI] [PubMed] [Google Scholar]
  2. Caspi R. R., Roberge F. G., Chan C. C., Wiggert B., Chader G. J., Rozenszajn L. A., Lando Z., Nussenblatt R. B. A new model of autoimmune disease. Experimental autoimmune uveoretinitis induced in mice with two different retinal antigens. J Immunol. 1988 Mar 1;140(5):1490–1495. [PubMed] [Google Scholar]
  3. Chader G. J., Wiggert B. Interphotoreceptor retinoid-binding protein. Characteristics in bovine and monkey retina. Vision Res. 1984;24(11):1605–1614. doi: 10.1016/0042-6989(84)90318-3. [DOI] [PubMed] [Google Scholar]
  4. Donoso L. A., Merryman C. F., Sery T. W., Shinohara T., Dietzschold B., Smith A., Kalsow C. M. S-antigen: characterization of a pathogenic epitope which mediates experimental autoimmune uveitis and pinealitis in Lewis rats. Curr Eye Res. 1987 Sep;6(9):1151–1159. doi: 10.3109/02713688709034888. [DOI] [PubMed] [Google Scholar]
  5. Dorey C., Cozette J., Faure J. P. A simple and rapid method for isolation of retinal S antigen. Ophthalmic Res. 1982;14(4):249–255. doi: 10.1159/000265199. [DOI] [PubMed] [Google Scholar]
  6. Eisenfeld A. J., Bunt-Milam A. H., Saari J. C. Uveoretinitis in rabbits following immunization with interphotoreceptor retinoid-binding protein. Exp Eye Res. 1987 Mar;44(3):425–438. doi: 10.1016/s0014-4835(87)80176-8. [DOI] [PubMed] [Google Scholar]
  7. Faure J. P. Autoimmunity and the retina. Curr Top Eye Res. 1980;2:215–302. [PubMed] [Google Scholar]
  8. Fox G. M., Kuwabara T., Wiggert B., Redmond T. M., Hess H. H., Chader G. J., Gery I. Experimental autoimmune uveoretinitis (EAU) induced by retinal interphotoreceptor retinoid-binding protein (IRBP): differences between EAU induced by IRBP and by S-antigen. Clin Immunol Immunopathol. 1987 May;43(2):256–264. doi: 10.1016/0090-1229(87)90133-4. [DOI] [PubMed] [Google Scholar]
  9. Gregerson D. S., Fling S. P., Obritsch W. F., Merryman C. F., Donoso L. A. Identification of T cell recognition sites in S-antigen: dissociation of proliferative and pathogenic sites. Cell Immunol. 1989 Oct 15;123(2):427–440. doi: 10.1016/0008-8749(89)90302-x. [DOI] [PubMed] [Google Scholar]
  10. Hirose S., Kuwabara T., Nussenblatt R. B., Wiggert B., Redmond T. M., Gery I. Uveitis induced in primates by interphotoreceptor retinoid-binding protein. Arch Ophthalmol. 1986 Nov;104(11):1698–1702. doi: 10.1001/archopht.1986.01050230136049. [DOI] [PubMed] [Google Scholar]
  11. Ikeda H., Taguchi O., Takahashi T., Itoh G., Nishizuka Y. L3T4 effector cells in multiple organ-localized autoimmune disease in nude mice grafted with embryonic rat thymus. J Exp Med. 1988 Dec 1;168(6):2397–2402. doi: 10.1084/jem.168.6.2397. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Iwasaki A., Yoshikai Y., Sakumoto M., Himeno K., Yuuki H., Kumamoto M., Sueishi K., Nomoto K. Sequential appearance of host-derived T cell subsets during differentiation in nude mice grafted with rat fetal thymus. J Immunol. 1990 Jul 1;145(1):28–35. [PubMed] [Google Scholar]
  13. Kojima A., Taguchi O., Nishizuka Y. Experimental production of possible autoimmune castritis followed by macrocytic anemia in athymic nude mice. Lab Invest. 1980 Apr;42(4):387–395. [PubMed] [Google Scholar]
  14. Kojima A., Tanaka-Kojima Y., Sakakura T., Nishizuka Y. Spontaneous development of autoimmune thyroiditis in neonatally thymectomized mice. Lab Invest. 1976 Jun;34(6):550–557. [PubMed] [Google Scholar]
  15. Kotake S., Wiggert B., Redmond T. M., Borst D. E., Nickerson J. M., Margalit H., Berzofsky J. A., Chader G. J., Gery I. Repeated determinants within the retinal interphotoreceptor retinoid-binding protein (IRBP): immunological properties of the repeats of an immunodominant determinant. Cell Immunol. 1990 Apr 1;126(2):331–342. doi: 10.1016/0008-8749(90)90325-l. [DOI] [PubMed] [Google Scholar]
  16. Rao N. A., Wacker W. B., Marak G. E., Jr Experimental allergic uveitis: clinicopathologic features associated with varying doses of S antigen. Arch Ophthalmol. 1979 Oct;97(10):1954–1958. doi: 10.1001/archopht.1979.01020020402028. [DOI] [PubMed] [Google Scholar]
  17. Redmond T. M., Wiggert B., Robey F. A., Nguyen N. Y., Lewis M. S., Lee L., Chader G. J. Isolation and characterization of monkey interphotoreceptor retinoid-binding protein, a unique extracellular matrix component of the retina. Biochemistry. 1985 Jan 29;24(3):787–793. doi: 10.1021/bi00324a038. [DOI] [PubMed] [Google Scholar]
  18. Sanui H., Redmond T. M., Hu L. H., Kuwabara T., Margalit H., Cornette J. L., Wiggert B., Chader G. J., Gery I. Synthetic peptides derived from IRBP induce EAU and EAP in Lewis rats. Curr Eye Res. 1988 Jul;7(7):727–735. doi: 10.3109/02713688809033202. [DOI] [PubMed] [Google Scholar]
  19. Sanui H., Redmond T. M., Kotake S., Wiggert B., Hu L. H., Margalit H., Berzofsky J. A., Chader G. J., Gery I. Identification of an immunodominant and highly immunopathogenic determinant in the retinal interphotoreceptor retinoid-binding protein (IRBP). J Exp Med. 1989 Jun 1;169(6):1947–1960. doi: 10.1084/jem.169.6.1947. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Smith H., Chen I. M., Kubo R., Tung K. S. Neonatal thymectomy results in a repertoire enriched in T cells deleted in adult thymus. Science. 1989 Aug 18;245(4919):749–752. doi: 10.1126/science.2788921. [DOI] [PubMed] [Google Scholar]
  21. Taguchi O., Kojima A., Nishizuka Y. Experimental autoimmune prostatitis after neonatal thymectomy in the mouse. Clin Exp Immunol. 1985 Apr;60(1):123–129. [PMC free article] [PubMed] [Google Scholar]
  22. Taguchi O., Nishizuka Y. Experimental autoimmune orchitis after neonatal thymectomy in the mouse. Clin Exp Immunol. 1981 Nov;46(2):425–434. [PMC free article] [PubMed] [Google Scholar]
  23. Taguchi O., Nishizuka Y., Sakakura T., Kojima A. Autoimmune oophoritis in thymectomized mice: detection of circulating antibodies against oocytes. Clin Exp Immunol. 1980 Jun;40(3):540–553. [PMC free article] [PubMed] [Google Scholar]
  24. Taguchi O., Nishizuka Y. Self tolerance and localized autoimmunity. Mouse models of autoimmune disease that suggest tissue-specific suppressor T cells are involved in self tolerance. J Exp Med. 1987 Jan 1;165(1):146–156. doi: 10.1084/jem.165.1.146. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Taguchi O., Takahashi T., Nishizuka Y. Self-tolerance and localized autoimmunity. Curr Opin Immunol. 1989;2(4):576–581. doi: 10.1016/0952-7915(90)90013-7. [DOI] [PubMed] [Google Scholar]
  26. Taguchi O., Takahashi T., Seto M., Namikawa R., Matsuyama M., Nishizuka Y. Development of multiple organ-localized autoimmune diseases in nude mice after reconstitution of T cell function by rat fetal thymus graft. J Exp Med. 1986 Jul 1;164(1):60–71. doi: 10.1084/jem.164.1.60. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Tung K. S., Smith S., Teuscher C., Cook C., Anderson R. E. Murine autoimmune oophoritis, epididymoorchitis, and gastritis induced by day 3 thymectomy. Immunopathology. Am J Pathol. 1987 Feb;126(2):293–302. [PMC free article] [PubMed] [Google Scholar]

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