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The Role of Fas-Fas Ligand–Mediated Apoptosis in Autoimmune Lacrimal Gland Disease in MRL/MpJ Mice

¹ From the Departments of Ophthalmology and ² Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland; and the ³ Department of Medicine, Wayne State University School of Medicine, Detroit, Michigan.

PURPOSE. MRL/MpJ mice spontaneously develop lacrimal gland inflammation and are a model for the human disorder Sjögren’s syndrome. MRL/MpJ-lpr/lpr (MRL/lpr) and MRL/Mp-+/+ (MRL/+) mice are congenic substrains, which differ only by a single autosomal recessive gene, the lpr mutation. This mutation results in defective Fas protein, defective lymphocytic apoptosis, and accelerated autoimmune lacrimal gland disease in MRL/lpr mice. We evaluated apoptosis in the lacrimal glands of MRL/lpr and MRL/+ mice.

METHODS. Inflammatory cells in the lacrimal glands of MRL/lpr and MRL/+ mice were evaluated for apoptosis with TUNEL staining and Fas and Fas ligand expression with immunohistochemistry.

RESULTS. MRL/lpr mice had a greater percentage of the lacrimal gland replaced by inflammatory infiltrate (30.3% ± 7.0%) than did MRL/+ mice (13.0% ± 3.0%, P = 0.02). However, similar amounts of lymphocytic apoptosis were present in the lacrimal glands of MRL/lpr and MRL/+ mice. The mean number of apoptotic cells per unit area of inflammation was 23.8 ± 2.4 in MRL/lpr mice and 24.6 ± 6.0 in MRL/+ mice (P = 0.91). Fas expression was absent on lymphocytes in MRL/lpr mice but was present on lymphocytes in MRL/+ mice. Fas ligand expression was present on epithelial structures in both substrains.

CONCLUSIONS. The accelerated lacrimal gland disease inflammation in MRL/lpr mice does not appear to be due to decreased apoptosis in the microenvironment of the lacrimal gland of MRL/lpr mice. It appears that in MRL/lpr mice there is defective extrathymic lymphoid apoptosis, permitting a relatively greater expansion of autoreactive T cells, which subsequently invade the lacrimal gland.

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