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S. R. Thurau, M. Diedrichs-Moehring, C. Hoffmann, G. Wildner; The Fate of Uveitogenic GFP+ T Cells in Rat EAU. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5201.
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To investigate the fate of GFP-transduced uveitogenic or non-pathogenic control CD4+ T cells after ocular inflammation, during spontaneous relapses as well as during experimental reinduction of disease and after extended remission.
GFP+ CD4+ T cells specific for the IRBP-peptide R14 were injected and rats developed uveitis 5-6 days later. At day 27 these rats were actively immunized with peptide R14 in CFA and developed a uveitis relapse around day 35. In another experiment GFP+ CD4+ T cells specific for Ovalbumin (OVA) were adoptively transferred to Lewis rats. Nine days later rats were immunized with retinal peptide PDSAg in CFA to induce uveitis. Eyes, lymph nodes and spleens were collected at different time points.
Six weeks after transfer GFP+ T cells of either specificity were observed in the retinas. In eyes with uveitis - either after spontaneous or induced relapse - the numbers of intraocular GFP+ cells increased slightly. Clusters of retina-specific GFP+ T cells were detectable, suggesting clonal expansion or focal attraction of new GFP+ cells invading from the periphery, whereas in clinically quiet eyes single GFP+ cells were distributed within the retina. OVA-specific T cells also migrated into the retina independently of EAU development, but never formed clusters in either active inflammation or quiescent stage. GFP+ cells were also found in peripheral lymph nodes (inguinal, mesenteric) and spleens more than 5 weeks after adoptive transfer. GFP+ cells were seen in the T cell areas of the spleen and in lymph nodes at any time during the observation period.
Activated T cells of any specificity can invade the ocular tissues and remain viable within the eyes and lymphoid tissues for an extended time period without undergoing apoptosis. They are recruited to the eye from the periphery during a secondary disease course, but may also clonally expand in situ after antigen-specific stimulation.
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