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G. Wildner, M. Diedrichs–Moehring; Reinduction of Experimental Autoimmune Uveitis in Lewis Rats . Invest. Ophthalmol. Vis. Sci. 2005;46(13):981.
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Purpose: Experimental autoimmune uveitis (EAU) in Lewis rats is regarded as an acute, monophasic disease, irrespective of its induction by active immunization with retinal antigen in complete Freund's adjuvant (CFA) or by adoptive transfer of activated CD4+ Th1 cells. Here we investigated whether the monophasic course is due to antigen–specific– or CFA–mediated immune regulation and tested different modalities to reinduce EAU. Methods: Lewis rats were immunized with S–Ag peptide PDSAg or IRBP peptide R14 in CFA or adoptively transferred with CD4+ T cells specific for said peptides. Uveitis was graded clinically, and 6 weeks later, after clinical signs of the first attack of disease had subsided, each group of rats was either immunized with PDSAg or R14 or adoptively transferred with PDSAg– or R14–specific T cells. Results: Primary induction of EAU with PDSAg/CFA immunization inhibited reinduction of disease, irrespective of the antigen and active or passive reinduction. This indicates not only antigen– or CFA–specific regulation, but also a "cross–suppression" or a bystander effect, in case of R14–specific T cells being transferred after PDSAg/CFA immunization. After primary EAU–induction with R14 in CFA disease could be reinduced by adoptive transfer of PDSAg– as well as R14–specific T cells. The primary induced EAU was always more severe than the recurrence. Conclusions: We have previously observed a differential regulation of PDSAg– and R14–specific immune responses in Lewis rats on the level of chemokines/–receptors. Here we show that PDSAg–specific, in contrast to R14–specific responses, induce a more efficient down–regulation of subsequently induced T cell responses.
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