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Ulrike Kaufmann, Maria Diedrichs-Möhring, Gerhild Wildner; Monophasic PDSAg-induced EAU dominates over relapsing R14-induced EAU. Invest. Ophthalmol. Vis. Sci. 2013;54(15):4521.
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© ARVO (1962-2015); The Authors (2016-present)
Rat EAU can be induced with S-Ag peptide PDSAg, inducing monophasic, or IRBP peptide R14, inducing relapsing uveitis. We have previously shown different dynamics of intraocular T cell populations during the two types of EAU, but the exact mechanisms behind the disease courses remain elusive. Here we used different combinations of the two antigens for immunization to investigate the mutual influence on the disease course and the immune response.
EAU was induced with PDSAg or R14 in CFA and with combinations of both, either administered separately at contralateral sides or as a mixture of both. Disease course was analyzed daily and cytokine pattern (IFN-γ, IL-17, IL-10) and Foxp3 expression of intraocular cells was determined at onset, peak, resolution and late remission of disease by flow cytometry. Data of the combined immunizations were compared with that from the conventional PDSAg and R14 immunizations.
While in R14-induced EAU 75% of the eyes developed relapses, none of the PDSAg- or PDSAg/R14-mixture immunized rats had recurrences. However, contralateral administration of both antigens allowed relapses in 12.5% of eyes. The cytokine pattern of intraocular cells looked similar in those animals immunized with both antigens, irrespective of the application, but differed from the pattern of the rats which were immunized with PDSAg or R14 only. Rats immunized with both antigens showed an R14-like cytokine pattern at onset of EAU and a PDSAg-like cytokine expression at resolution of EAU. Cultivated lymph node cells of mixture-immunized rats had increased numbers of Foxp3+, but decreased IFN-γ+ cells compared to rats immunized with PDSAg or R14 only, respectively.
Disease course and cytokine pattern of intraocular cells confirmed a dominant role of the monophasic, PDSAg-specific immune response. Increased regulatory T cells expressing IL-10 or Foxp3 might be responsible for the prevention of relapses.
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