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Ellen J. Lee, Hyun Kim, Stephen R. Planck, James T. Rosenbaum, Holly L. Rosenzweig; In Vivo Imaging Of T Cell Trafficking In Eyes During Spondyloarthritis. Invest. Ophthalmol. Vis. Sci. 2012;53(14):6900.
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Uveitis, or intraocular inflammation, frequently occurs in patients with spondyloarthropathies such as ankylosing spondylitis (AS). Little is understood of the ocular component of these diseases. We previously used a murine model of spondyloarthropathy, wherein autoimmunity to a cartilage proteoglycan (PG) results in uveitis coincident with arthritis and spondylitis, to demonstrate a critical regulatory role for IFNγ in suppressing the Th17 response that contributes to uveitis in this model. Here, we focus on the in vivo T cell trafficking responses within the eye throughout the course of spondyloarthropathy in mice lacking IFNγ, wherein an exacerbated uveitis and Th17 response ensue.
We crossed transgenic mice to yield IFNγ-deficient mice bearing DsRed2 fluorescent, PG-specific T cells. These mice were immunized i.p. with PG (n = 25 mice) or adjuvant alone (n = 4 mice). Using intravital videomicroscopy, we monitored the T cell trafficking responses within distinct eye tissues (iris, limbus, cornea) out to 6 weeks post immunization. The concurrent severity of arthritis was graded using a clinical scoring system.
Intravital videomicroscopy revealed no change in the number of T cells across all eye tissues examined in control, adjuvant-treated mice. In PG-immunized mice, increased rolling and adherence along the iris microvasculature coinciding with extravasation into the iris tissue was observed with average initial onset at ~22d, when minimal clinical arthritis was present. Despite progressive arthritis, we unexpectedly found that the presence of T cells within the iris was episodic in that it increased and regressed over a span of 7-14d. The severity and onset of the T cell response in one eye did not necessarily correspond or coincide with that of the contralateral eye. T cells preferentially accumulated in the limbus, even in control mice. In response to PG immunization, the number of T cells in the limbus was increased at 10d, which preceded their accumulation in the iris. While most of the T cells were visualized within the limbus and iris, some T cells were also detected within the cornea, wherein their presence peaked at 21d post immunization and was episodic akin to that in the iris.
Our data reveal unanticipated dynamics of T cell trafficking within the eye during progressive spondyloarthritis. Investigation of T cell trafficking responses in the presence of IFNγ is underway. Future studies of how the presence of autoreactive T cells in uveitic eyes relates to disease in other target organs should be informative to multisystem diseases such as AS.
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