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J. D. Pitcher, III, C. S. De Paiva, S. Pangelinan, K. C. Yoon, W. J. Farley, M. E. Stern, D.-Q. Li, S. C. Pflugfelder; Spontaneous T Cell Mediated Auto-Immune Lacrimal Keratoconjunctivitis in CD25 Knock-Out Mice. Invest. Ophthalmol. Vis. Sci. 2008;49(13):431.
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To investigate function and immunopathology in the lacrimal function unit of IL-2Rα -/- (CD25KO) mice.
The ocular surface of 8- and 12-week old CD25KO mice was evaluated. Corneal smoothness was evaluated by reflection of a ring light. Conjunctival goblet cell density was counted in PAS stained sections. Immunohistochemistry evaluated CD4 and CD8 T cell infiltration of the conjunctival and lacrimal gland. T helper (Th)-1, 2 and 17 associated cytokines were evaluated by real time PCR.
Compared to 8-week old C57BL6 mice, 8-week old CD25KO mice had a significant decrease in goblet cell density, and corneal smoothness. They also developed a significant increase in number of CD4+ T and CD8+T cells infiltrating the lacrimal gland and in the goblet cell rich area of the conjunctiva; however, the CD4/CD8 ratio was significantly elevated. These changes in CD25KO mice were even more pronounced at 12 weeks of age. CD25KO mice showed higher levels of MMP-9, IL-17, IL-23, IL-6, TGF-β1, IL-2, IL-13, IL-4, IFN-γ and lower levels of IL-12 mRNA transcripts in their conjunctiva compared to C57BL/6 mice controls.
Disruption of IL-2 signaling in mice by CD25 knockout results in auto-immune lacrimal keratoconjunctivitis that mimics the ocular surface pathology of Sjögren’s syndrome. A predominance of Th-2 and Th-17 cytokines were detected in the conjunctiva.
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