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G. Wildner, M. Diedrichs-Möhring, C. von Toerne, P. J. Nelson, D. Voehringer; Two Different Types of Eau in a Single Strain of Rats. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4766.
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© ARVO (1962-2015); The Authors (2016-present)
Experimental autoimmune uveitis (EAU) in Lewis rats can be induced with S-Ag peptide PDSAg or IRBP peptide R14, resulting in two differently regulated diseases. We investigated the differences in the diseases as well as in peptide-specific T cell lines.
EAU was induced either by immunization with peptides in CFA, adoptive transfer of activated T cell lines or GFP-transduced T cell lines to follow the fate of the cells in vivo. Nippostrongylus brasiliensis infection to induce a Th2 shift was done 10 days before immunization. T cell lines were obtained from lymph node cells of immunized rats by repeated restimulation in vitro. MHC class II restriction was tested using RT1.B or RT1.D and B7 cotransfected mouse mastocytoma cell lines as APC. PDSAg- and R14-specific T cell lines were analyzed by gene arrays and quantitative RT-PCR for differential gene expression.
While EAU induced with PDSAg was acute and monophasic, R14-mediated disease was spontaneously relapsing or could be experimentally reinduced. Tracing GFP+ T cells showed prolonged intraocular survival of R14-, but not PDSAg-specific T cells. Both T cell lines express a Th1 type cytokine profile, while R14-specific T cells secrete higher amounts than PDSAg-specific cells. However, N. brasiliensis infection significantly reduced R14-, but enhanced PDSAg-induced disease. PDSAg-specific T cells are RT1.B-, R14-specific cells RT1.D-restricted, and gene array analysis revealed enhanced expression of genes related to antigen-presentation, adhesion and cell interaction and inhibition of apoptosis in R14-specific T cells compared to PDSAg-specific lines.
In the same strain of rats two different ocular autoantigen peptides induce two types of disease differing with respect to clinic and immune regulation, potentially reflecting the human situation.
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