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S.-M. Hsu, R. Mathew, J. Stein-Streilein; In vitro-Generated Tolerogenic Antigen Presenting Cells Suppress Ongoing Experimental Autoimmune Uveoretinitis. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4834.
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It is well known that even mild uveitis will damage the ocular structure and decrease visual acuity. Experimental autoimmune uveoretinitis (EAU) in mice is a model of human uveitic disease. The eye and the peripheral immune system cooperate in a model known as anterior chamber-associated immune deviation (ACAID) to prevent intraocular inflammation. The eye-derived antigen presenting cells (APC) are central to the development of ACAID and acquire their tolerogenic capacity partly because of their exposure to TGFβ2 in the aqueous humor. Others have shown that exposure of APC to TGFβ in vitro mimicked eye-derived APC in ACAID. We postulated that TGFβ treated APC exposed to autoantigens would suppress autoimmune inflammation, EAU, in mice.
EAU was induced with interphotoreceptor retinoid-binding protein (IRBP)1-20 in C57BL/6 mice. Tolerogenic APC (Tol APC) were prepared by culturing splenic APC with IRBP1-20 and TGFβ2. Seven days after induction of EAU, IRBP-specific Tol APC were injected intravenously. Inflammation of the retina was evaluated twice a week for 5 weeks. To test for the presence and phenotype of regulatory T (Treg) cells in Tol APC-treated mice, CD4+ and/or CD8+ T cells from spleens will be transferred to naïve mice and then immunized with IRBP1-20 for EAU induction.
Mice that received IRBP immunization and treated with Tol APC showed a significant delay in disease onset and a lower clinical EAU score. The Tol APC-treated group also had a lower incidence of EAU than the control group.
Treatment of mice with IRBP-pulsed Tol APC after their immunization suppressed the incidence and severity of EAU in mice. As in ACAID, the suppression is expected to correlate with the presence of antigen specific CD8+ Treg cells induced by the in vitro generated Tol APC. Adoptive transfer of enriched splenic T cells from treated mice will determine if the suppression is induced by an ACAID-like antigen specific Treg cell.
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