A new model of experimental autoimmune keratoconjunctivitis sicca (KCS) induced in Lewis rat by the autoantigen Klk1b22.
OBJECTIVE
This study was designed to generate an inducible autoimmune model of keratoconjunctivitis sicca (KCS) for study of pathogenesis of the disease.


METHODS
Lewis rats were immunized with a mixture of lacrimal and salivary gland extract or recombinant mouse protein kallikrein 1b22 (Klk1b22) emulsified in complete Freund's adjuvant (CFA). For disease induction by adoptive transfer of primed cells, donor rats were received with T-cell blasts. KCS were observed by either clinical signs or histology.


RESULTS
The autoantigen Klk1b22, isolated from the lacrimal and salivary glands, readily induced Sjögren's syndrome (SS)-like KCS in the recipients. The diseased animals presented the clinical and pathologic symptoms that resemble related human disease. Most immunized rats showed an increase, then a decrease in tear volume, together with corneal opacity and ocular lesions. Histologic examination revealed that the rats displayed the cardinal signs of primary SS-like 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 more severe disease with earlier onset.


CONCLUSIONS
Klk1b22 is an autoantigen for inducing an experimental SS-like KCS in Lewis rats. The availability of this new and reproducible rat model should provide a new and needed tool for studying the pathogenesis of SS.
Jiang
Guomin
G
Department of Ophthalmology and Visual Sciences, Kentucky Lions Eye Center, School of Medicine, University of Louisville, Louisville, Kentucky 40202, USA.
Ke
Yan
Y
Sun
Deming
D
Li
Hao
H
Ihnen
Mark
M
Jumblatt
Marcia M
MM
Foulks
Gary
G
Wang
Yali
Y
Bian
Yang
Y
Kaplan
Henry J
HJ
Shao
Hui
H
D019264:Adoptive Transfer; D000818:Animals; D001323:Autoantibodies / Q000097:blood; D001324:Autoantigens / Q000276:immunology* / Q000302:isolation & purification; D001327:Autoimmune Diseases / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D015551:Autoimmunity; D001762:Blepharitis / Q000276:immunology / Q000473:pathology; D015153:Blotting, Western; D004195:Disease Models, Animal; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007124:Immunoenzyme Techniques; D007610:Kallikreins / Q000276:immunology* / Q000302:isolation & purification; D007634:Keratitis / Q000276:immunology / Q000473:pathology; D007638:Keratoconjunctivitis Sicca / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D007765:Lacrimal Apparatus / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D016133:Polymerase Chain Reaction; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000494:pharmacology; D012469:Salivary Glands / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013601:T-Lymphocytes / Q000276:immunology; D013666:Tears / Q000378:metabolism
D001323:Autoantibodies; D001324:Autoantigens; D011994:Recombinant Proteins; D007610:Kallikreins; C540490:kallikrein 1b22, mouse