Age-related T-cell cytokine profile parallels corneal disease severity in Sjogren's syndrome-like keratoconjunctivitis sicca in CD25KO mice

Rheumatology (Oxford). 2010 Feb;49(2):246-58. doi: 10.1093/rheumatology/kep357. Epub 2009 Dec 9.


Objectives: IL-2ralpha (CD25)(-/-) mice develop autoimmunity and lymphoproliferative disorders, including SS-like disease. The objective of this study was to evaluate the severity of corneal epithelial disease and T-cell cytokine profile in the ocular surface tissues of CD25KO mice.

Methods: CD25KO mice were evaluated at 8, 12 and 16 weeks of age. Corneal epithelial smoothness and corneal permeability were measured. Phenotype of infiltrating lymphocytes was evaluated by immunohistochemistry. Th-1, -2 and -17 associated factors were measured by real-time PCR in cornea and conjunctiva and by Luminex immunobead assay in tears.

Results: Compared with 8-week-old wild-type (WT) mice, CD25KO mice of the same age had significantly greater corneal irregularity and a significant increase in the number of CD4(+) and CD8(+) T cells infiltrating the conjunctiva. CD25KO mice had significantly higher levels of IL-6, TGF-beta1, IL-23R, IL-17A, IL-17F, IL-21, CCL20, IL-10, GATA-3 and IFN-gamma mRNA transcripts in their cornea and conjunctiva than WT mice at 8 weeks. IL-17A and IL-17F mRNA transcripts peaked at 12 weeks, whereas IFN-gamma spiked at 16 weeks in CD25KO mice. Increased expression of IL-17A and IL-17F at 12 weeks in CD25KO mice was accompanied by a worsening of corneal surface parameters and an increase of CD4(+) T cell infiltrating the cornea.

Conclusions: Disruption of IL-2 signalling in CD25KO mice results in age-dependent SS-like autoimmune lacrimal-keratoconjunctivitis. A mix of Th-1 and Th-17 cytokines was detected. The peak severity of corneal epithelial disease corresponded to the peak of IL-17 expression.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / immunology
  • Animals
  • Apoptosis
  • Conjunctiva / immunology
  • Cornea / immunology
  • Cytokines / metabolism*
  • Epithelium, Corneal / immunology*
  • Epithelium, Corneal / pathology
  • Epithelium, Corneal / physiopathology
  • Inflammation Mediators / metabolism
  • Interleukin-2 Receptor alpha Subunit / deficiency
  • Interleukin-2 Receptor alpha Subunit / immunology
  • Keratoconjunctivitis Sicca / immunology*
  • Keratoconjunctivitis Sicca / pathology
  • Keratoconjunctivitis Sicca / physiopathology
  • Lacrimal Apparatus / immunology
  • Lacrimal Apparatus / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Permeability
  • Sjogren's Syndrome / immunology*
  • Sjogren's Syndrome / pathology
  • Sjogren's Syndrome / physiopathology
  • T-Lymphocyte Subsets / immunology*
  • Tears / immunology


  • Cytokines
  • Il2ra protein, mouse
  • Inflammation Mediators
  • Interleukin-2 Receptor alpha Subunit