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M.E. Stern, S.C. Pflugfelder, K.F. Siemasko, J. Gao, R.M. Corrales, C.S. De Paiva, J.Y. Niederkorn; Desiccating Stress to the Ocular Surface Induces a Transferable T–Cell Mediated Lacrimal Keratoconjunctivitis . Invest. Ophthalmol. Vis. Sci. 2006;47(13):3530.
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Chronic dry eye, such as seen in Sjögren’s syndrome, is associated with T cell infiltration of the lacrimal gland and conjunctiva. The purpose of this study was to determine if T cells from mice exposed to a desiccating environment were capable of inducing dry eye when adoptively transferred to naïve mice.
C57BL/6 wild type (WT) female mice were exposed to 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) (Dursun et al.; IOVS 2002) for 5 days. CD4+ T cells were isolated from the superficial cervical lymph nodes (CLN) of the DS donors by magnetic cell isolation. One CLN donor equivalent of CD4+ T cells (2 X 106 cells) was injected IP into syngeneic T–cell deficient nude mouse recipients kept under non stressed conditions. Globes with lid attached were collected 3 days after the adoptive transfer and stained with hematoxylin and eosin or anti–mouse CD4+ antibody.
DS treatment of C57BL/6 WT mice resulted in decreased tear production, reduced conjunctival goblet cell numbers, and conjunctival CD4+ T cell infiltration. Adoptive transfer of DS donor CLN CD4+ T cells to athymic recipients resulted in a significant reduction in tear production and increased cellular infiltration into the lacrimal functional unit (LFU; conjunctiva, cornea, and lacrimal glands) but not other organs. Immunohistochemistry confirmed CD4+ T cell infiltration in the LFU of adoptive cell transfer recipients. Athymic recipients of CD4+ cells from non stressed donors had normal tear production and no detectable LFU cellular infiltration. Adoptive transfer of DS CD4+ T cells into WT mice produced moderately severe disease, implying an inhibitory effect of CD4+CD25+ T regulatory cells in the WT recipient. In vivo depletion of CD25+ cells in WT recipients using a monoclonal anti–CD25 antibody prior to the adoptive transfer of CD4+ T cells from DS donors resulted in significantly greater LFU cellular infiltration and a 57% decrease in tear production.
These results suggest that ocular surface desiccation initiates a CD4+ T cell mediated inflammatory response to shared epitopes of the LFU components. This model confirms that the immune–based inflammation in dry eye is mediated by CD4+ T cells and under normal circumstances, is mitigated by CD4+CD25+ T regulatory cells.
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