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S. R. Thurau, M. Diedrichs-Möhring, I. Rädler-Angeli, G. Wildner; Induction of ACAID and Oral Tolerance With S-Antigen Peptide and Mimotopes in Rat EAU. Invest. Ophthalmol. Vis. Sci. 2009;50(13):830.
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ACAID and oral tolerance induction are two potential ways to prevent experimental uveitis. In our Lewis rat model of EAU we have previously described two mimotopes of retinal S-Antigen peptide PDSAg, which are derived from environmental antigens: Rota from rotavirus and Cas from bovine milk casein. Both, Rota and Cas, are pathogenic but lack oral tolerogenicity. Here we investigate whether these peptides can induce ACAID for the prevention of EAU.
ACAID was induced by a single intracameral injection of saline (control), PDSAg, Rota or Cas 7 days before immunization. For oral tolerance induction the same antigens were fed three times every other day, with the last oral treatment 2-3 days prior to immunization. EAU was induced with PDSAg or Rota, respectively, in CFA. Disease was graded clinically and histologically.
ACAID as well as oral tolerance induced by PDSAg almost completely suppressed EAU, while Rota or Cas did not ameliorate PDSAg-induced EAU, independently of mode of application. In the model of EAU induction with Rota, intraocular Rota injection could not reduce EAU severity, whereas intraocular PDSAg effectively ameliorated uveitis severity.
Pathogenic antigens/peptides in EAU are not necessarily tolerogenic, neither for the induction of oral tolerance nor for ACAID. Our data indicate that in both pathways of tolerance induction the regulatory T cells can differ from the effector population with respect to antigen recognition.
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