The “classical” EAU model induced by immunization of mice with the retinal protein
IRBP or its peptides has been very useful to study basic mechanisms of ocular inflammation,
but is inadequate for some types of studies due to the need for active immunization in the
context of strong bacterial adjuvants. We generated transgenic (Tg) mice on the B10.RIII
background that express a T cell receptor (TCR) specific for IRBP161-180. Three strains of
TCR Tg mice were established. Spontaneous uveitis developed in two of the three strains by
2-3 months of age. Susceptibility correlated with a higher copy number of the transgenic TCR
and a higher proportion of TCR Tg T cells in the peripheral repertoire. Even in mice with
uveitis, peripheral IRBP-specific CD4+ T cells displayed mostly a naïve phenotype. In contrast, T cells
infiltrating uveitic eyes mostly showed an effector/memory phenotype, and included Th1, Th17 as well as T
regulatory cells. These mice thus provide a new and distinct model of uveitis from the “classical” EAU, and may
represent some types of uveitis more faithfully. Importantly, this new transgenic model of uveitis can serve as a
template for therapeutic manipulations, and as a source of naïve retina-specific T cells for a variety of basic
and pre-clinical studies. Several examples of such studies will be discussed.
Keywords: Autoimmunity, uveitis, EAU, animal model, Th1, Th17.
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