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

胚胎大鼠胸腺移植（TG）在其肾包膜（TG裸鼠）下可以纠正胸腺BALB/c裸鼠的t细胞功能。然而，多种器官局限性自身免疫性疾病，包括甲状腺炎和干燥综合征样疾病，在大鼠胸腺移植后1个月左右在TG裸小鼠中自发发生。在唾液腺、泪腺和角膜出现严重炎性病变，表现为干燥综合征样疾病。涎腺炎、泪腺炎和角膜炎的发生率分别为90%、95%和70%。严重的病变通常见于泪腺。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唾液腺和泪腺IgG型抗体。显微镜检查显示角膜表面不规则，角膜新生血管明显，间质混浊。角膜炎的角膜有明显的浸润，包括淋巴细胞浸润、间质新生血管和角化的浅表上皮细胞。在角膜炎裸鼠血清中检测到抗角膜上皮细胞IgG型抗体。免疫印迹分析显示，在非还原和还原条件下，分别识别出可溶性185 kD蛋白和42、47、49和50kD蛋白。这些病变可通过脾CD4阳性细胞转移到裸鼠身上。通过注射针对CD4分子的单克隆抗体，可以很好地预防和治愈这些病变。

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.