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(Investigative Ophthalmology and Visual Science. 2006;47:249-255.)
© 2006 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.05-0774

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Alpha-internexin as a Corneal Autoantigen in Spontaneous Autoimmune Keratitis Mouse Model

Takaaki Hattori,1,2 Masaru Takeuchi,1 Katsuhiro Ohno,2,3 Midori Ogawara,4 Tetsuya Asatani,1 Yoshihiko Usui,1 Ryuji Muramatsu,1 Masaki Inagaki,5 Masahiko Usui,1 and Osamu Taguchi2

1From the Department of Ophthalmology, Tokyo Medical University, Tokyo, Japan; Divisions of 2Molecular Pathology and 5Biochemistry, Aichi Cancer Center Research Institute, Nagoya, Japan; 3Shiroyama Park Dental Clinic, Nagoya, Japan; and 4Department of Neurophysiology, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.

PURPOSE. The purpose of this study was to identify target antigens of autoimmune keratitis with a disease-prone mouse model.

METHODS. BALB/c nude mice grafted with embryonic rat thymi (TG nude mice) develop various organ-localized autoimmune lesions, including keratitis. A hybridoma producing a monoclonal antibody (OT-20), specific for corneal epithelium was established by using spleen cells from this model mouse of keratitis, and the target of OT-20 was identified by immunoblot analysis. Then, using the antigen, T-cell proliferation and cytokine production by TG nude mice with keratitis were examined.

RESULTS. Immunoblot analysis revealed {alpha}-internexin to be the target antigen of OT-20 that specifically recognizes corneal epithelium. Sera from TG nude mice with keratitis reacted with {alpha}-internexin on Western blot analysis, and the T cells of these mice on stimulation with {alpha}-internexin exhibited proliferation responses and produced IL-2, IFN-{gamma}, and TNF-{alpha}, but not IL-4 or IL-5.

CONCLUSIONS. These results suggest that {alpha}-internexin is one of the corneal antigens associated with keratitis, developing spontaneously in TG-nude mice, with a probable pathogenic role.





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