Jiang Guomin, Ke Yan, Sun Deming, Li Hao, Ihnen Mark, Jumblatt Marcia M, Foulks Gary, Wang Yali, Bian Yang, Kaplan Henry J, Shao Hui
Department of Ophthalmology and Visual Sciences, Kentucky Lions Eye Center, School of Medicine, University of Louisville, Louisville, Kentucky 40202, USA.
Invest Ophthalmol Vis Sci. 2009 May;50(5):2245-54. doi: 10.1167/iovs.08-1949. Epub 2008 Dec 5.
This study was designed to generate an inducible autoimmune model of keratoconjunctivitis sicca (KCS) for study of pathogenesis of the disease.
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.
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.
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.
本研究旨在建立一种可诱导的干燥性角结膜炎（KCS）自身免疫模型，以研究该疾病的发病机制。
用泪腺和唾液腺提取物或重组小鼠蛋白激肽释放酶1b22（Klk1b22）与完全弗氏佐剂（CFA）乳化后的混合物免疫Lewis大鼠。为通过致敏细胞的过继转移诱导疾病，给供体大鼠输入T细胞母细胞。通过临床症状或组织学观察KCS。
从泪腺和唾液腺分离出的自身抗原Klk1b22能轻易在受体中诱导出类似干燥综合征（SS）的KCS。患病动物呈现出与人类相关疾病相似的临床和病理症状。大多数免疫大鼠泪液量先增加后减少，同时伴有角膜混浊和眼部病变。组织学检查显示，大鼠表现出原发性SS样KCS的主要特征，包括泪腺和唾液腺明显的淋巴细胞浸润以及腺泡细胞的破坏。免疫荧光研究表明，CD8(+)和CD4(+) T细胞均大量浸润，前者在受损导管中占主导。最后，Klk1b22反应性T细胞的过继转移诱导出更严重且发病更早的疾病。
Klk1b22是在Lewis大鼠中诱导实验性SS样KCS的自身抗原。这种新的、可重复的大鼠模型的建立应为研究SS的发病机制提供一种新的、必要的工具。
