May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Klk1b22, a Protein of Tissue Kallikrein Family, Induced Experimental Autoimmune Keratoconjunctivitis Sicca (KCS) in Lewis Rats
Author Affiliations & Notes
  • H. Shao
    Dept of Ophthal & Visual Sciences, University of Lousiville, Louisville, Kentucky
  • G. Jiang
    Dept of Ophthal & Visual Sciences, University of Lousiville, Louisville, Kentucky
  • Y. Ke
    Dept of Ophthal & Visual Sciences, University of Lousiville, Louisville, Kentucky
  • H. Li
    Dept of Ophthal & Visual Sciences, University of Lousiville, Louisville, Kentucky
  • M. Ihnen
    Dept of Ophthal & Visual Sciences, University of Lousiville, Louisville, Kentucky
  • M. Jumblatt
    Dept of Ophthal & Visual Sciences, University of Lousiville, Louisville, Kentucky
  • G. Foulks
    Dept of Ophthal & Visual Sciences, University of Lousiville, Louisville, Kentucky
  • Y. Wang
    Dept of Ophthal & Visual Sciences, University of Lousiville, Louisville, Kentucky
  • Y. Bian
    Dept of Ophthal & Visual Sciences, University of Lousiville, Louisville, Kentucky
  • H. J. Kaplan
    Dept of Ophthal & Visual Sciences, University of Lousiville, Louisville, Kentucky
  • D. Sun
    Dept of Ophthal & Visual Sciences, University of Lousiville, Louisville, Kentucky
  • Footnotes
    Commercial Relationships  H. Shao, None; G. Jiang, None; Y. Ke, None; H. Li, None; M. Ihnen, None; M. Jumblatt, None; G. Foulks, None; Y. Wang, None; Y. Bian, None; H.J. Kaplan, None; D. Sun, None.
  • Footnotes
    Support  Supported in part by NIH grants EY12974, EY14599, EY014366, EY017373, R24 EY015636 and RBP career development award (HS).
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 193. doi:https://doi.org/
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      H. Shao, G. Jiang, Y. Ke, H. Li, M. Ihnen, M. Jumblatt, G. Foulks, Y. Wang, Y. Bian, H. J. Kaplan, D. Sun; Klk1b22, a Protein of Tissue Kallikrein Family, Induced Experimental Autoimmune Keratoconjunctivitis Sicca (KCS) in Lewis Rats. Invest. Ophthalmol. Vis. Sci. 2008;49(13):193. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : To generate an Ag inducible autoimmune model of KCS for studying the autoimmune-mediated pathogenesis of the disease.

Methods: : Lewis rats were immunized with the protein extracts of mouse salivary and lacrimal glands. KCS was monitored by clinical and pathologic examinations. The pathogenic autoantigen in the protein extracts were fractioned by Sephacryl S-200 column. Each fraction containing disease inducing antigen was further determined using a combination of T cell proliferation assay and disease induction. The single band of protein which induced the disease was further identified by mass spectrometry analysis. A recombinant protein, Klk1b22, was generated and the pathogenic activity of this protein was determined. Inflammatory cells infiltrated into the lacrimal glands were identified by immunohistochemical staining.

Results: : Klk1b22, a molecular mass at 30 kDa, is a protein member of tissue kallikrein family. Immunization to Lewis rats with the recombinant protein of Klk1b22 readily induced KCS in the recipient rats. The diseased animals showed the clinical and pathological symptoms that resemble related human disease. Immunized rats showed an increase, followed by a decrease in tear volume, corneal opacity and other ocular lesions. Histological examination revealed that the diseased rats displayed the cardinal signs of primary KCS, including marked lymphocytic infiltration of the lacrimal and salivary glands and destruction of the acinar cells. Immunofluorescence studies showed that both CD8+ and CD4+ T cells were heavily infiltrated, with the former cells predominant in the damaged ducts. Finally, adoptive transfer of Klk1b22-reactive T cells induced severer disease than those induced by Ag immunization.

Conclusions: : Our results indicate that Klk1b22 is an autoantigen that can induce KCS in Lewis rat. The availability of this new and reproducible rat model should provide us with a useful tool for studying the pathogenesis of KCS.

Keywords: autoimmune disease • lacrimal gland • inflammation 
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