Sjogren's syndrome (SS) is a chronic, progressive autoimmune disease that most prominently affects the salivary and lacrimal glands. The disease can also produce systemic manifestations and is associated with systemic autoimmunity. The data are strong that SS is more common than any autoimmune rheumatic illness, except rheumatoid arthritis. The ultimate goal of the investigator's laboratory is to understand the mechanisms by which autoimmunity occurs and produces immune-mediated diseases such as SS. Immunizing with short peptides from 60 kD Ro, the PI has developed an animal model of SS that recapitulates not only the clinical and pathological manifestations including salivary gland lymphocytic infiltrate but also recapitulates the serologic manifestations including anti-Ro/SSA and anti-La/SSB. No other animal model of the disease reproduces the pathological and serological findings of human SS with such fidelity. In general, the PI hypothesizes that characterization of this animal model, which so closely mimics the human disease will lead to important insights into the genetics, and immunology of SS. In particular, the PI hypothesizes that the glandular infiltrates found in these animals will contain T and B lymphocytes with certain homing receptors and specificity for the Ro or La autoantigens. In the first specific aim this hypothesis will be tested by determining the phenotype and specificity of the lymphocytic infiltrate found in the salivary glands of the new animal model of Sjogren's syndrome.
In Specific Aim 2 the lymphocyte subset and the adhesion phenotype critical for the development of disease in the peptide-induced model of Sjogren's syndrome will be determined using an adoptive transfer model and taking advantage of selected genetically manipulated mice. In the third specific aim the PI will test the hypothesis that disease can be prevented with immature dendritic cell immunization. The work is important to public health because Sjogren's syndrome is a common disease but under diagnosed. The disease is poorly understood. Presently, the only available treatments are simply supportive and/or symptomatic. Improved understanding of the disease at a fundamental level is possible through study of animal models. Such understanding may lead to improved recognition and treatment.
