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Y. Cui, H. Shao, C. Lan, H. J. Kaplan, Sr., D. Sun; Intraocular Injection of an Uveitogenic Peptide Suppressed the Generation of Il-17+ Pathogenic T Cells. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4773.
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Intraocular injection of antigen induced impaired capacity of the recipient animals to mount an effective immune response which has been designated as anterior chamber associated immune deviation (ACAID). The suppressive mechanism of anterior chamber associated immune deviation (ACAID) remained largely unclear. Our recent studies demonstrated that IL-17+ autoreactive T cells and the T cells expressing γΔ TCR play a major role in the pathogenesis of EAU, we therefore wished to determine whether intraocular inoculation of a pathogenic peptide would affect the development of IFN-γ+ and IL-17+ pathogenic T cells in EAU. We have also examined whether thus induced immune suppression is antigen specific and whether the intraocular injection of antigen at different compartments (anterior chamber, intravitreous, and subretinal injection) is important for induction of immune tolerance.
Experiments were conducted in B6 mouse. The uveitogenic peptide (IRBP1-20) was administered through the AC, intravitreous or subretina. Seven days after the injection; the mice were primed with a pathogenic dose of the IRBP1-20 in adjuvant. 13 days later, T cells isolated from spleens and draining lymph nodes were cultured, the pathogenic activity of the T cells isolated from treated and untreated animals were compared and the Th1 and Th17 responses measured.
Intraocular injection of the uveitogenic peptide (IRBP1-20), but not the non-uveitogenic (IRBP161-180) peptide significantly suppressed the IL-17 response. IRBP-specific T cells isolated from the treated mice have greatly decreased pathogenic activity. Depletion of γΔ T cell abolished the intraocularly induced tolerance.
Our results show that administration of an uveitogenic peptide into the AC inhibits development of IL17+ uveitogenic T-cell responses and the γΔ T cell response, which was associated with decreased activation and pathogenic activity of the induced autoreactive T cells.
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