Alpha-internexin as a corneal autoantigen in spontaneous autoimmune keratitis mouse model

Invest Ophthalmol Vis Sci. 2006 Jan;47(1):249-55. doi: 10.1167/iovs.05-0774.

Abstract

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.

MeSH terms

  • Animals
  • Antibodies, Monoclonal
  • Autoantibodies / blood
  • Autoantigens / immunology*
  • Autoimmune Diseases / immunology*
  • Autoimmune Diseases / pathology
  • Blotting, Western
  • Carrier Proteins / genetics
  • Carrier Proteins / immunology*
  • Cytokines / biosynthesis
  • Disease Models, Animal*
  • Epithelium, Corneal / immunology*
  • Female
  • Fluorescent Antibody Technique, Indirect
  • Hybridomas
  • Intermediate Filament Proteins / genetics
  • Intermediate Filament Proteins / immunology*
  • Keratitis / immunology*
  • Keratitis / pathology
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Recombinant Proteins
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes / immunology

Substances

  • Antibodies, Monoclonal
  • Autoantibodies
  • Autoantigens
  • Carrier Proteins
  • Cytokines
  • Intermediate Filament Proteins
  • Recombinant Proteins
  • alpha-internexin