ROLE OF T-CELLS IN THE PATHOGENESIS OF AUTOIMMUNE LACRIMAL GLAND DISEASE IN MRL MP-LPR/LPR MICE/

Purpose. MRL/Mp-lpl/lpr mice (MRL/lpr) spontaneously develop an autoim mune disease, including lacrimal gland lesions, which are a model for Sjogren's syndrome. Target organ lesions in MRL/lpr mice are composed largely of CD4+ T cells, and treatment with monoclonal antibodies (mAb ) against CD4 improves in the systemic autoimmune disease but not the lacrimal gland inflammation. In anti-CD4 mAb-treated MRL/lpr mice, the lacrimal gland lesions are composed largely of CD8+ T cells. The effe cts of depletion of: (1) all T cells; (2) both CD4+ and CD8+ T cells, and (3) only CD8+ T cells on the lacrimal gland disease were investiga ted. Methods. MRL/lpr mice underwent neonatal thymectomy and were trea ted with weekly injections of 6 mg of anti-Thy 1 mAb from age one week until sacrifice at age five months. Control nonthymectomized mice und erwent similar Treatment with either saline or normal rat immunoglobul in (rIg) injections. In a second experiment, MRL/lpr mice were treated with weekly injections of either: (1) 2 mg anti-CD4 mAb and 5 mg anti -CD8; or (2) 5 mg anti-CD8 alone. Control mice underwent similar treat ment with either saline or rIg injections. Results. Combined treatment with neonatal thymectomy and anti-Thy 1 mAb was effective in reducing the lacrimal gland disease in both frequency (50% greater than or equ al to grade 3 vs. 100% in controls, P < 0.002) and extent (median 0% o f lacrimal gland area involved by inflammation vs. 14.8% in controls; P = 0.01). Combined anti-CD4 and anti-CD8 therapy also was effective i n reducing the lacrimal gland disease in terms of frequency (25% grade 3 vs. 93% in controls; P = 0.002) and extent (median 0% of lacrimal g land involved by inflammation vs. 12.9% in controls; P = 0.0005). Trea tment with anti-CD8 mAb therapy alone was ineffective. The systemic au toimmune disease was also improved by T cell depletion and by combined anti-CD4 and anti-CD8 mAb therapy but not by anti-CD8 mAb therapy alo ne. Conclusions. Suppression of both CD4+ and CD8+ T cells is required to suppress lacrimal gland inflammation in MRL/lpr mice.