PARADOXIC EFFECT OF ANTI-CD4 THERAPY ON LACRIMAL GLAND DISEASE IN MRLMP-LPR/LPR MICE/

Purpose. MRL/Mp-lpr/lpr mice (MRL/lpr) spontaneously develop lacrimal gland inflammatory lesions and are a model for the human disease Sjogr en's syndrome. Therapy with monoclonal antibodies (mAb) to CD4 amelior ates the autoimmune renal, vasculitic, and intraocular inflammatory le sions in MRL/lpr mice. The effect of anti-CD4 mAb therapy on lacrimal gland immunopathology was evaluated. Methods. From 1 to 5 months of ag e, MRL/lpr mice were treated with weekly intraperitoneal injections of 2 mg anti-CD4 mAb, after which they were killed and their lacrimal gl ands were removed for histologic evaluation and immunocytochemistry. C ontrol mice were administered weekly intraperitoneal injections of eit her saline or normal rat immunoglobulin. Results. Anti-CD4 mAb treatme nt produced no reduction in lacrimal gland inflammation but did change its morphology. In control mice, there were multiple sharply delineat ed foci of inflammatory cells in the lacrimal gland, whereas in anti-C D4 mAb-treated mice, there was a more diffuse inflammation surrounding ill-defined foci that spread throughout the gland. Immunocytochemistr y revealed that in control mice, lesions were composed predominantly o f CD4+ T cells, but in anti-CD4 mAb-treated mice, CD8+ T cells predomi nated. Conclusions. Although anti-CD4 mAb therapy of MRL/lpr mice elim inated autoimmune renal disease, autoantibody formation, and ocular in flammatory disease, it had a paradoxic effect on lacrimal gland lesion s. Lacrimal gland lesions in the anti-CD4 mAb-treated mice were not de creased, but they had a different morphology and a different immunocyt ochemical profile.