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