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Prophylactic Effect of IL-10 Gene Transfer on Induced Autoimmune Dacryoadenitis

¹From the Doheny Eye Institute and the ²Departments of Cell and Neurobiology, ³Ophthalmology, ⁴Physiology and Biophysics, and ⁶Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California; and the ⁵Institute of Medical Immunology, Humboldt University, Berlin, Germany.

PURPOSE. To evaluate the effect of viral IL-10 on the lacrimal gland immunopathologic response in the ocular surface disease, induced autoimmune dacryoadenitis.

METHODS. Disease was induced in rabbits by injecting inferior lacrimal glands with peripheral blood lymphocytes activated by 5 days of coculture with autologous acinar cells in a mixed-cell reaction. In the treated group, an adenoviral vector carrying the vIL-10 gene was concurrently injected with activated lymphocytes. Tears were collected periodically for quantitation of IL-10 by ELISA. Two weeks after disease induction, tear production, tear film breakup time, and rose bengal staining score were determined. Sectioned glands were immunostained for expression of CD4, CD8, rabbit thymic lymphocyte antigen (RTLA), CD18 and major histocompatibility complex class II.

RESULTS. The titer of vIL-10 in tears was at its maximum on day 3, started to decline by day 7, and was undetectable by day 14. In the diseased group, the tear production rate and tear film breakup time were significantly decreased, and rose bengal staining was significantly increased. Diseased glands had immune cell infiltrates containing CD4⁺, RTLA⁺, and CD18⁺ cells, and major histocompatibility complex class II expression was increased. These changes were significantly ameliorated by expression of vIL-10.

CONCLUSIONS. In vivo transduction of the lacrimal gland with AdvIL-10 resulted in the transient appearance of vIL-10 in tears. The presence of vIL-10 partially suppressed the appearance of Sjögren-syndrome–like features of reduced tear production, accelerated tear breakup, ocular surface disease, and immunopathologic response. Anti-inflammatory cytokine gene expression may offer a therapeutic modality for the treatment of autoimmune dacryoadenitis, once suitable vectors become available.

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