Role of t cell subsets in lacrimal gland disease in MRL/Mp-Iprllpr mice

Purpose. MRL/Mp-lpr/lpr mice (MRL/lpr) spontaneously develop an autoimmune disease, including lacrimal gland lesions, which are a model for Sjögren's syndrome. Target organ lesions in MRL/lpr mice are composed largely of CD4+ T cells, and Ireatment 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 effects of depletion of. 1 ) only CD8+ T cells and 2) both CD4+ and CD8+ T cells on the lacrimal gland disease were investigated. Methods. 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 treatment with either saline or rig injections. Results. Combined anti-CD4 and anti-CD8 therapy was effective in 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 gland involved by inflammation vs 12 9% in controls, P=0.0005). Treatment with anti-CD8 mAb therapy alone was ineffective. The systemic autoimmune disease was also improved by combined antiCD4 and anti-CD8 mAb therapy but not by anti-CD8 mAb therapy aJone. Conclusions. Suppression of both CD4+ and CD8+ T cells is required to suppress lacrimal gland inflammation in MRL/lpr mice. CD4-CD8- TCR cc/β+ "double negative" T cells, which are massively increased in number in the lymph nodes of MRL/lpr mice, do not appear to contribute to the lacrimal gland disease.