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Study of animal model of autoimmune Sjogren syndrome with keratitis sicca.

自身免疫性干燥综合征干燥性角膜炎动物模型的研究。

基本信息

批准号：
05670216
负责人：
TAGUCHI Osamu
金额：
$ 1.41万
依托单位：
Aichi Cancer Center Research Institute
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1994
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05670216/
关键词：
Sjogre syndrome Keratitis sicca nude mouse Thymus Autoimmune disease Dacryadenitis シェーグレン症候群

项目摘要

T-cell function of athymic BALB/c nude mice can be corrected by embryonic rat thymus grafts (TG) under their renal capsule (TG nude mice). However, multiple organ-localized autoimmune diseases, including thyroiditis and Sjogren syndrome like disease, develop spontaneously in TG nude mice at around 1-month after rat thymus grafting. Severe inflammatory lesions found in salivary gland, lacrimal gland and cornea as Sjogren syndrome like disease. The incidence of sialoadenitis, dacryadenitis and keretitis was 90%, 95% and 70%, respectively. Severe lesions were usually found in the lacrimal glands. The lesion was characterized by serious disturbances in the secretion of the epithelial cells, associated with massive infiltration of lymphocytes. Anti-salivary gland and lacrimal gland antibodies of IgG type were detected in the sera of mice with sialoadenitis and dacryadenitis, respectively. Microscopic examination of these eyes showed irregular corneal surfaces, marked corneal neovascularization and stromal opacification. The cornea with keratitis revealed marked infiltration involving lymphocytic infiltration, stromal neovascularization and keratinized superficial epithelial cells. Anti-corneal epithelial cell antibodies of IgG type were detected in the sera of TG nude mice with keratitis. Immunoblotting assay under non-reducing and reducing conditions showed that a soluble 185 kD and 42,47,49, and 50kD proteins were recognized, respectively. These lesions can be transferred to nude mice by splenic CD4 positive cells. These lesions can be perfectly prevented and cured by injection of monoclonal antibody against CD4 molecule.

裸鼠肾被膜下的胚胎大鼠胸腺移植(TG裸鼠)可纠正裸鼠的T细胞功能。然而，在大鼠胸腺移植后1个月左右，包括甲状腺炎和干燥综合征样病在内的多器官局限性自身免疫性疾病在TG裸鼠体内自发发展。唾液腺、泪腺和角膜出现严重炎性病变，为干燥综合征样疾病。涎腺炎、泪腺炎和肾炎的发生率分别为90%、95%和70%。严重病变多见于泪腺。病变的特点是上皮细胞分泌严重紊乱，伴有大量淋巴细胞浸润。在涎腺炎和泪腺炎小鼠血清中分别检测到抗涎腺抗体和泪腺抗体。显微镜检查这些眼睛显示不规则的角膜表面，明显的角膜新生血管和基质混浊。角膜炎的角膜有明显的浸润性改变，包括淋巴细胞浸润、间质新生血管和角化的表浅上皮细胞。在角膜炎裸鼠血清中检测到IgG型抗角膜上皮细胞抗体。在非还原和还原条件下的免疫印迹分析表明，可溶性蛋白分别为185kD、42、47、49和50kD。这些病变可以通过脾中的CD4阳性细胞转移到裸鼠体内。这些病变可以通过注射抗CD4分子的单抗来完全预防和治愈。