Alpha-internexin as a corneal autoantigen in spontaneous autoimmune keratitis mouse model.
OBJECTIVE
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.
Hattori
Takaaki
T
Department of Ophthalmology, Tokyo Medical University, Tokyo, Japan.
Takeuchi
Masaru
M
Ohno
Katsuhiro
K
Ogawara
Midori
M
Asatani
Tetsuya
T
Usui
Yoshihiko
Y
Muramatsu
Ryuji
R
Inagaki
Masaki
M
Usui
Masahiko
M
Taguchi
Osamu
O
D000818:Animals; D000911:Antibodies, Monoclonal; D001323:Autoantibodies / Q000097:blood; D001324:Autoantigens / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology; D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D019573:Epithelium, Corneal / Q000276:immunology*; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006825:Hybridomas; D007381:Intermediate Filament Proteins / Q000235:genetics / Q000276:immunology*; D007634:Keratitis / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011994:Recombinant Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D001324:Autoantigens; D002352:Carrier Proteins; D016207:Cytokines; D007381:Intermediate Filament Proteins; D011994:Recombinant Proteins; C046643:alpha-internexin