Lacrimal gland inflammation in MRL/Mp-lpr/lpr mice: Both CD4+ and CD8+ T cells induce autoimmune disease

Purpose. MRL/Mp-lpr/lpr mice (MRL/lpr) spontaneously develop widespread autoimmune disease, including lacrimal gland lesions, which are a model for Sjögren's syndrome. While the lymph nodes in MRL/lpr mice are composed largely of double negative T cells, the lacrimal gland lesions are composed primarily of CD4+ T cells with lesser numbers of CD8+ T cells and B cells. MRL/lpr mice were treated with monoclonal antibody (mAb) to CD4, combined neonatal thymectomy and mAb to Thy1, or cyclosporine (CSA) to determine the effect on the lacrimal gland disease. Methods. Groups of 10 to 15 mice were treated chronically with one of three regimens: 1) weekly intraperitoneal (IP) injections of 2 mg of anti-CD4 mAb; 2) combined neonatal thymectomy and weekly IP injections of 6 mg anti-Thy1 (total T cell depletion); or daily IP injections of 2 mg of CSA. Controls consisted of one group of mice injected with saline and one group of mice injected with either normal rat immunoglobulin (for mAb experiments) or CSA diluent. Treatment was continued until sacrifice at five months age. Results. All three treatment regimens resulted in marked reduction of the systemic autoimmune disease, including the lymphoproliferation, vasculitis, glomerulonephritis, and serologic abnormalities. Control mice had extensive lacrimal gland disease. 100% of control mice had grade 3 or 4 lesions, and the mean percent lacrimal gland involved by inflammation was 16.1% to 19.7%. Anti-CD4 mAb therapy did not diminish lacrimal gland disease but resulted in lesions composed largely of CD8+ T cells. T cell depletion and CSA treatment both resulted in improvement of lacrimal gland disease. The percent animals with grade 3 or 4 lesions were 50% (p<0.002) and 23% (p<0.0001), respectively; and the mean percent areas involved were 5.5% (p=0.01) and 4.7% (p=0.0003). Conclusions. Depletion of both CD4+ and CD8+ T cells appears to be required for prevention of lacrimal gland lesions in MRL/lpr mice. CSA is also effective for the treatment of lacrimal gland disease in MRL/lpr mice.