A New Model of Experimental Autoimmune Keratoconjunctivitis Sicca (KCS) Induced in Lewis Rat by the Autoantigen Klk1b22

被引:31
作者
Jiang, Guomin [1 ]
Ke, Yan [1 ]
Sun, Deming [1 ]
Li, Hao [1 ]
Ihnen, Mark [1 ]
Jumblatt, Marcia M. [1 ]
Foulks, Gary [1 ]
Wang, Yali [1 ]
Bian, Yang [1 ]
Kaplan, Henry J. [1 ]
Shao, Hui [1 ]
机构
[1] Univ Louisville, Dept Ophthalmol & Visual Sci, Kentucky Lions Eye Ctr, Louisville, KY 40292 USA
关键词
RESEMBLING SJOGRENS-SYNDROME; IQI/JIC MICE; IMMUNOHISTOCHEMICAL CHARACTERIZATION; GLANDULAR KALLIKREIN; TISSUE KALLIKREIN; IMMUNE-RESPONSE; MOUSE MODEL; T-CELLS; DISEASE; SIALADENITIS;
D O I
10.1167/iovs.08-1949
中图分类号
R77 [眼科学];
学科分类号
100212 ;
摘要
PURPOSE. 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 Sjorgren'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. (Invest Ophthalmol Vis Sci. 2009;50:2245-2254) DOI:10.1167/iovs.08-1949
引用
收藏
页码:2245 / 2254
页数:10
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