April 2010
Volume 51, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2010
Immunopathogenesis in a Mouse Model of Lacrimal Keratoconjunctivitis is Antigen Specific
Author Affiliations & Notes
  • K. F. Siemasko
    Biological Sciences, Allergan, Inc, Irvine, California
  • C. S. Schaumburg
    Biological Sciences, Allergan, Inc, Irvine, California
  • M. Calonge
    Ocular Surface Group-IOBA, IOBA-University Of Valladolid, Valladolid, Spain
  • V. L. Calder
    Ocular Biology and Therapeutics, UCL Institute of Ophthalmology, London, United Kingdom
  • J. Y. Niederkorn
    Ophthalmology, UT SW-Medical Center, Dallas, Texas
  • C. S. De Paiva
    Ocular Surface Center, Cullen Eye Institute, Baylor College of Medicine, Houston, Texas
  • S. C. Pflugfelder
    Ocular Surface Center, Cullen Eye Institute, Baylor College of Medicine, Houston, Texas
  • M. E. Stern
    Biological Sciences, Allergan, Inc, Irvine, California
  • Footnotes
    Commercial Relationships  K.F. Siemasko, Allergan, Inc., E; C.S. Schaumburg, Allergan, Inc., E; M. Calonge, Allergan, Inc., C; V.L. Calder, Allergan, Inc., C; J.Y. Niederkorn, Allergan, Inc., C; C.S. De Paiva, None; S.C. Pflugfelder, Allergan, Inc., C; M.E. Stern, Allergan, Inc., E.
  • Footnotes
    Support  None.
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 3395. doi:
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      K. F. Siemasko, C. S. Schaumburg, M. Calonge, V. L. Calder, J. Y. Niederkorn, C. S. De Paiva, S. C. Pflugfelder, M. E. Stern; Immunopathogenesis in a Mouse Model of Lacrimal Keratoconjunctivitis is Antigen Specific. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3395.

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Abstract

Purpose: : To determine if experimental ALKC is antigen-specific. We hypothesized that DO-11.10 DS pathogenic CD4+ T cells would not be able to adoptively transfer disease to nude T-cell deficient mice because the T cells from these mice would not be able to recognize an ALKC putative antigen (eg. Klk13).

Methods: : Ova-TCR transgenic mice (DO-11.10) were exposed to desiccating stress for 10 days to determine if a dry eye response was elicited in these mice. BALB/c wild type (WT) or DO11.10 female mice were exposed to a desiccating environmental stress (DS; subcutaneous scopolamine injections, humidity <40%, and air flow across wire meshed screened cages) for 5 days. Control or 5 day DS mouse spleen and superficial cervical lymph node CD4+ T cells were IP injected into nude T cell deficient mouse recipients. Additionally, mice were treated with topical Klk13 or OVA. Tears and ocular surface tissues were collected for Luminex and histopathological analysis, respectively.

Results: : Luminex analysis was done to determine tear cytokine levels from BALB/c WT or DO-11.10 donors and recipients. BALB/c WT mice exposed to 5 days DS had tear levels that were significantly higher than BALB/c WT control for IFN-γ, IL-12(p70), and TNF-α. These cytokines were not increased in the tears of DO-11.10 mice exposed to DS for 5 days. Adoptive transfer of 5 day DS BALB/c WT CD4+ T cells resulted in significantly higher levels of IFN-γ, IL-1α, and TNF-α. Adoptive transfer of DO-11.10 CD4+ T cells did not result in any statistically significant increases in cytokines in the tears. Inflammatory cell migration into the conjunctiva was only detected in recipient mice receiving BALB/c WT 5 day DS CD4+ T cells. Mice topically challenged with Klk13 displayed an ALKC phenotype. However, topical challenge with OVA did not induce ALKC disease pathology.

Conclusions: : Ova-restricted T cells do not mediate ocular surface inflammation suggesting that experimental ALKC is antigen specific.

Keywords: antigen presentation/processing • cytokines/chemokines • inflammation 
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