May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Spontaneous T Cell Mediated Auto-Immune Lacrimal Keratoconjunctivitis in CD25 Knock-Out Mice
Author Affiliations & Notes
  • J. D. Pitcher, III
    Ocular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, Texas
  • C. S. De Paiva
    Ocular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, Texas
  • S. Pangelinan
    Ocular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, Texas
  • K. C. Yoon
    Ocular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, Texas
  • W. J. Farley
    Ocular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, Texas
  • M. E. Stern
    Allergan Inc, Irvine, California
  • D.-Q. Li
    Ocular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, Texas
  • S. C. Pflugfelder
    Ocular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, Texas
  • Footnotes
    Commercial Relationships  J.D. Pitcher, None; C.S. De Paiva, None; S. Pangelinan, None; K.C. Yoon, None; W.J. Farley, None; M.E. Stern, Allergan, Inc, E; D. Li, None; S.C. Pflugfelder, Allergan, Inc, C.
  • Footnotes
    Support  NIH Grants EY11915 (SCP), EY016928-01(CSDP), RPB, Oshman Foundation, William Stamps Farish Fund, Hamill Foundation and Allergan
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 431. doi:https://doi.org/
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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. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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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 
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