Desiccating stress induces T cell-mediated Sjögren's Syndrome-like lacrimal keratoconjunctivitis

J Immunol. 2006 Apr 1;176(7):3950-7. doi: 10.4049/jimmunol.176.7.3950.


Chronic dry eye syndrome affects over 10 million people in the United States; it is associated with inflammation of the lacrimal gland (LG) and in some cases involves T cell infiltration of the conjunctiva. We demonstrate that environmental desiccating stress (DS) elicits T cell-mediated inflammation of the cornea, conjunctiva, and LG, but not other organs in mice. The lacrimal keratoconjunctivitis (LKC) was mediated by CD4(+) T cells, which, when adoptively transferred to T cell-deficient nude mice, produced inflammation in the LG, cornea, and conjunctiva, but not in any other organ. Adoptively transferred CD4(+) T cells produced LKC even though recipients were not exposed to DS. LKC was exacerbated in euthymic mice depleted of CD4(+)CD25(+)forkhead/winged helix transcription factor(+) regulatory T cells. The results suggest that DS exposes shared epitopes in the cornea, conjunctiva, and LG that induce pathogenic CD4(+) T cells that produce LKC, which under normal circumstances is restrained by CD4(+)CD25(+)forkhead/winged helix transcription factor(+) regulatory T cells.

Publication types

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

MeSH terms

  • Animals
  • Cell Movement
  • Dehydration / complications
  • Dehydration / physiopathology*
  • Desiccation
  • Female
  • Forkhead Transcription Factors / metabolism
  • Keratoconjunctivitis Sicca / immunology*
  • Keratoconjunctivitis Sicca / pathology
  • Lacrimal Apparatus / immunology
  • Lacrimal Apparatus / pathology*
  • Mice
  • Sjogren's Syndrome / immunology*
  • Sjogren's Syndrome / pathology
  • Stress, Physiological / etiology
  • Stress, Physiological / physiopathology*
  • T-Lymphocytes / immunology*


  • Forkhead Transcription Factors
  • Foxp3 protein, mouse