Sjogren's syndrome in man is characterized by dry mouth and eyes often leading to stomatitis, increased incidence of caries and periodontal disease, and severe ocular problems. The salivary and lacrimal glands are infiltrated by T and B lymphocytes and antibodies to organ specific antigens can be found in the serum of patients with the disease. Experimental autoallergic sialadenitis (EAS) in the Lewis (LEW) rat shares many histopathologic features with Sjogren's syndrome and will serve as our model for the study of pathogenetic factors in the disease. It is hypothesized that EAS is due to the exposure of cell associated molecules in salivary tissues to an altered or poorly regulated immune system. This exposure, in turn, initiates a T cell mediated, autoimmune response that leads to the destruction of the salivary parenchyma. We have confirmed the reproducibility of the LFW rat model of EAS and now propose to use it to answer the following questions: 1) What is the nature of the target antigen(s) in EAS? 2) Where is the target antigen(s) in EAS located? 3) What are the abnormalities in the cellular and/or the humoral immune system that are important in the pathogenesis of EAS? 4) Can procedures that modify and/or alter the immune system affect the induction or induce reversal of EAS? We will improve the induction and immunization protocol and determine if there are clinical symptoms that correlate with the lymphocytic infiltrates seen in the glands. We will identify, isolate and localize the target antigen(s) immunocytochemically and by using established cell fractionation and protein purification techniques. Immunological analysis will include: identification and characterization of the autoantibodies and mononuclear cells present in the glands during EAS; attempts to induce the disease by adoptive transfer of immune cells and/or serum, and; attempts to inhibit the disease by modulation of the immune system and/or the target antigen(s) with monoclonal antibodies or immunomodulating agents. These results should provide a comprehensive analysis of EAS in LEW rats and may provide important insights into the pathogenesis of Sjogren's syndrome in man.
| Cutler, L S; Rozenski, D; Coolens, J et al. (1991) Experimental autoallergic sialadenitis in the LEW rat. I. Parameters of disease induction. Cell Immunol 135:335-45 |
| Greiner, D L; Angelillo, M; Wayne, A L et al. (1991) Experimental autoallergic sialadenitis in the LEW rat. III. Role of CD4+ T cells in EAS induction. Cell Immunol 135:354-9 |
| Cutler, L S; Greiner, D L; Rozenski, D (1991) Experimental autoallergic sialadenitis in the LEW rat. II. Target antigens are associated with cell surface and intracellular particulate fractions derived from the submandibular gland. Cell Immunol 135:346-53 |
