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Y. De Kozak, S. Camelo, F. Rolling, M.-C. Naud, B. Thillaye-Goldenberg, C. Verwaerde; Reduction of Experimental Autoimmune Uveoretinitis (EAU) by Intracameral Injection of AAV2/2-GFP Through Antigen Nonspecific Regulation of the Immune Response. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5207.
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Despite ocular immune privilege, intraocular inflammation develops and is a frequent cause of visual loss. Antigens introduced into the anterior chamber of the eye contribute to deviant immune response. Recently, viral infections have been shown to regulate immune response through activation of regulatory T (Tregs) cells. These data prompted us to examine the effect of intracameral injection of AAV2/2 expressing GFP on S-Ag-induced EAU in rat.
Intracameral injection of AAV2/2-GFP or saline was performed in Lewis rats 5 weeks before footpad injection of S-Ag in complete Freund's adjuvant. Histopathology, immunostaining, lymphocyte proliferation and cytokine titration were performed 21 days after immunization. Passive transfer experiments were done by injection of cells collected from AAV2/2-GFP-treated rats immunized with S-Ag into recipients that were simultanously immunized. Presence of Tregs was checked either by immunostaining or by RT-PCR in different organs.
Rats injected with AAV2/2-GFP into the anterior chamber showed GFP expression in iris epithelium, in ciliary body stromal cells with dendritic form, in corneal endothelial cells. Intracameral injection of AAV2/2-GFP significantly reduced EAU compared to rats injected with saline whereas intravitreal injection of AAV2/2-GFP had no such effect. CD4+CD25+ and CD25+Foxp3+ cells were detected in the eyes from AAV2/2-GFP-treated rats compared to saline-injected rats. Injection of AAV2/2-GFP decreased lymphocyte proliferation to S-Ag and IFN-g production compared to saline-injected rats. RT-PCR analysis of draining lymph nodes and spleen revealed an increased expression of TGF-b, Foxp-3, CTLA-4 mRNA. Finally, a transfer of protection was achieved by injecting lymph node or spleen cells from AAV2/2-GFP-treated rats immunized with S-Ag into S-Ag immunized recipients.
Our results suggest that Tregs, possibly ocular antigen nonspecific, activated by the danger signal induced by AAV and/or the presence of a nonself Ag in the anterior chamber of the eye, could reduce EAU through a bystander fashion.
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