An experimental model of autoimmune dacryoadenitis has been developed which involves the induction of lacrimal gland disease by immunizing rats to an organ-specific antigen. The objectives of the proposed research are to use this established rat model to elucidate the basic immunopathologic mechanisms in the induction of this ocular disease and to develop methods to prevent or suppress ocular autoimmune disease by generating suppressor cells. Using in vitro activation and passive transfer experiments, attempts will be made to define the pathogenic mechanisms that cause this autoimmune disease. Specifically, these studies will analyze more precisely the role of T cell subsets, macrophages, or B cells in harmful immune reactions. In addition, genetic susceptibility or resistance of this autoimmune disease will be examined using different strains of rats to identify particular immune response genes that may be involved in the pathogenesis of lacrimal autoimmunity. The rat model of autoimmune dacryoadenitis provides a practical tool for exploring approaches to treatment. One therapeutic approach will be the use of Cyclosporine A, since this drug has specific anti-T cell activities. We will assess the efficacy of Cyclosporine in the treatment or prevention of autoimmune dacryoadenitis. A second and more ideal approach would be to activate antigen-specific suppressor cells. This will be attempted using syngeneic cell-bound antigen to augment T suppressor cell generation. the physiologic role played by suppressor cells in abrogating the undesirable immune reactions leading to dacryoadenitis will be studied. In recent experiments we have detected a lacrimal gland protein that potentiates the IgA immune response. Whether this protein and the autoantigen described above are identical requires further studies. This question will be answered when precise structural characterization of these two proteins has been achieved and their functions analyzed using biochemical, immunologic, and pathologic criteria. Furthermore, the mode of action of this IgA- potentiating factor on T or B target cells will be explored. These studies may explain the preponderance of IgA plasma cells in the lacrimal gland.

National Institute of Health (NIH)
National Eye Institute (NEI)
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Visual Sciences A Study Section (VISA)
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Johns Hopkins University
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Liu, S H; Zhou, D H; Gottsch, J D et al. (1993) Treatment of experimental autoimmune dacryoadenitis with cyclosporin A. Clin Immunol Immunopathol 67:78-83
Liu, S H; Zhou, D H; Franklin, R M (1993) Lacrimal gland-derived lymphocyte proliferation potentiating factor. Invest Ophthalmol Vis Sci 34:650-7
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Liu, S H; Zhou, D H (1992) Experimental autoimmune dacryoadenitis: purification and characterization of a lacrimal gland antigen. Invest Ophthalmol Vis Sci 33:2029-36
Gottsch, J D; Liu, S H; Stark, W J (1992) Mooren's ulcer and evidence of stromal graft rejection after penetrating keratoplasty. Am J Ophthalmol 113:412-7
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Liu, S H; Prendergast, R A; Silverstein, A M (1987) Experimental autoimmune dacryoadenitis. I. Lacrimal gland disease in the rat. Invest Ophthalmol Vis Sci 28:270-5
Liu, S H; Prendergast, R A; Silverstein, A M (1986) Experimental immunogenic granuloma of the orbit: transfer of granulomatous hypersensitivity with a subset of T lymphocytes. Invest Ophthalmol Vis Sci 27:70-6