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C. Terrada, B. Bodaghi, Y. de Kozak, S. Fisson, P. LeHoang, D. Klatzmann, B. Salomon; Antigen Specific CD4+CD25+ Regulatory T–Cells Modulate Intraocular Inflammation in a Model of Experimental Uveoretinitis Induced by a Neoretinal Antigen . Invest. Ophthalmol. Vis. Sci. 2006;47(13):5153.
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We have previously described a murine model of experimental uveoretinitis. Regulatory T cells play a role in this model. In this study, we have compared the therapeutic effects of polyclonal versus antigen specific CD4+CD25+ regulatory T cells after intravenous or intravitreal injection .
In mice expressing hemagglutinin (HA) in the retina after subretinal injection of rAAV, uveitis was induced by intravenous administration of 2 x 106 activated HA–specific T cells. These cells were obtained from purified Thy–1.1 TCR–HA CD25– cells and stimulated by irradiated BALB/c splenocytes and HA peptide for 4 days. At the same time or 4 days later, HA–specific or polyclonal BALB/c CD4+CD25+ T cells were injected intravenously or intravitreally. A challenge was performed by intravenous activated HA–specific effector T cells, 21 days after the induction of uveitis. Intraocular inflammation was clinically and histologically studied in all animals.
CD4+CD25+ T cells controlled uveitis only if they were specific for the target antigen (HA). Compared to intravenous injection, the effect observed after intravitreal injection was obtained with low number of cells.Furthermore, protection against a challenge was achieved only after local administration of HA–specific regulatory T cells.
Regulation of experimental uveoretinitis may be obtained by using CD4+CD25+ T–cells. Specificity and activation status of these cells should be further analyzed in order to develop new in situ therapeutic strategies.
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