The role of Fas-Fas ligand-mediated apoptosis in autoimmune lacrimal gland disease in MRL/MpJ mice.
OBJECTIVE
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.
Jabs
D A
DA
Department of Ophthalmology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. djabs@jhmi.edu
Lee
B
B
Whittum-Hudson
J
J
Prendergast
R A
RA
D000818:Animals; D017209:Apoptosis; D001327:Autoimmune Diseases / Q000378:metabolism* / Q000473:pathology; D053222:Fas Ligand Protein; D007124:Immunoenzyme Techniques; D020287:In Situ Nick-End Labeling; D007765:Lacrimal Apparatus / Q000378:metabolism / Q000473:pathology; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D019463:Mice, Inbred MRL lpr; D012859:Sjogren's Syndrome / Q000378:metabolism* / Q000473:pathology; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology*; D019014:fas Receptor / Q000378:metabolism*
C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D019014:fas Receptor