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M. E. Stern, S. C. Pflugfelder, K. F. Siemasko, J. Gao, V. L. Calder, M. Calonge, J. Y. Niederkorn; The Ocular Surface Plays an Antigenic Role in the Initiation of a Mouse Model of Dry Eye Disease. Invest. Ophthalmol. Vis. Sci. 2008;49(13):188.
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© ARVO (1962-2015); The Authors (2016-present)
To determine if immunization with conjunctival or corneal epithelial cell suspensions from mice exposed to a dry, desiccating environment will induce pathogenic CD4+ T cells that can produce dry eye disease when adoptively transferred to athymic mice.
C57BL/6 wild type (WT) female mice were exposed to a desiccating environmental stress (DS; subcutaneous scopolamine injections (0.5 mg/0.2 ml) TID, humidity <40%, and air flow by fans across wire meshed screened cages) for 10 days. Anti-CD25 antibody treated C57BL/6 WT mice were immunized by hind footpad injection in the presence of CFA with control or DS conjunctiva (1 X 106) or cornea (7 X 105) epithelial cells. After 5 days, 5 X 106 spleen and cervical lymph node CD4+ T cells from immunized mice were injected IP into syngeneic T-cell deficient athymic recipients kept under non-stressed conditions. Recipient mice were sacrificed four days later and tissues were collected. Immunized and recipient tears were collected for detection of inflammatory cytokines using Luminex technology.
The immunized mice had a minimal response as evaluated by tear production, histology, and tear cytokine levels. However, CD4+ cells from mice immunized with DS cornea epithelial cells had a statistically significant increase in IL-12, IL-1β and TNF-α tear levels as compared to mice receiving the control cornea CD4+ cells. A statistically significant (*P=0.025) cellular infiltration into conjunctiva of recipient mice receiving CD4+ cells from mice immunized with DS conjunctiva epithelial cells was detected. There was significant cellular infiltration of both mononuclear cells (*P=0.014) and neutrophils (*P=0.001) into the conjunctiva of athymic recipient mice receiving CD4+ T cells from immunized mice that were injected with DS cornea cells. Adoptive transfer of CD4+ cells from immunized mice receiving control conjunctiva or cornea epithelial cells did not induce high cytokine tear levels in recipient mice.
The results from the athymic recipient mice confirm that DS conjunctiva and cornea epithelial cells contain an antigenic determinant which is capable of generating pathogenic CD4+ T cells. Conjunctival and corneal epithelial cells exposed to a dry, desiccating environment have the capacity to initiate a CD4+ mediated immune response that is transferable.
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