Spontaneous T Cell Mediated Auto-Immune Lacrimal Keratoconjunctivitis in CD25 Knock-Out Mice

Abstract

Purpose: : To investigate function and immunopathology in the lacrimal function unit of IL-2Rα -/- (CD25KO) mice.

Methods: : 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.

Results: : 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.

Conclusions: : 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.

Keywords: cornea: tears/tear film/dry eye • inflammation • cytokines/chemokines