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

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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.