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Z. Zhu, D. Stevenson, J.E. Schechter, A.K. Mircheff, T. Ritter, M.D. Trousdale; Prophylactic Effect of IL-10 Gene Expression in a Rabbit Model of Induced Autoimmune Dacryoadenitis . Invest. Ophthalmol. Vis. Sci. 2003;44(13):2517.
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Purpose: To evaluate the effect of viral IL-10 expression on lacrimal gland immunopathology and ocular surface disease resulting from induced autoimmune dacryoadenitis. Methods: Autoimmune dacryoadenitis was induced in rabbits by injecting the lacrimal glands with peripheral blood lymphocytes (PBL) activated by 5 days of co-culture with autologous acinar cells in a mixed cell reaction (ID group). In the treated group, an adenoviral vector carrying the Epstein Barr virus IL-10 gene (AdvIL-10), was concurrently injected with the activated PBL (ID/AdvIL-10). Tear production was monitored by Schirmer test and tears were collected for detection of vIL-10 transgene product by ELISA. Tear film break-up time (BUT) and rose bengal staining were studied to evaluate the ocular surface changes. Frozen sections of the glands were immunostained for CD4, CD8, rabbit thymic lymphocyte antigen (RTLA), and CD18 antigen expression. Results: Basal tear production and tear BUT declined and rose Bengal staining scores increased 2weeks after disease induction, indicating keratoconjunctivitis sicca in the ID group. Focal mononuclear infiltrates were found between acini in the lacrimal glands and around ducts and venules, some of which assumed the high endothelial phenotype. The immune infiltrates characteristically contained increased numbers of CD4+, RTLA+ and CD18+ cells. In the group that received concurrent gene therapy, the IL-10 titers were at a maximum on day 3, declining by day 7 and absent by day 14. A significant improvement was observed in the clinical assessments and compared to the ID group, the lacrimal glands had significantly decreased numbers of CD4+, CD18+ and RTLA+ cells, while the number of CD8+ cells in the infiltrate increased. Conclusions: In vivo transduction of the lacrimal gland with AdvIL-10 resulted in transient expression in the gland and the appearance of IL-10 protein in tears. The presence of IL-10 protein partially suppressed the appearance of Sjögren's syndrome-like features of reduced tear production, tear breakup time, ocular surface disease and the immunohistopathological findings associated with induced autoimmune dacryoadenitis, Immunoregulatory cytokine gene transfer offers a potential therapeutic modality for the treatment of autoimmune dacryoadenitis.
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