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Yan Ke, Deming Sun, Ping Zhang, Guomin Jiang, Henry J. Kaplan, Hui Shao; Suppression of Established Experimental Autoimmune Uveitis by Anti-LFA-1α Ab. Invest. Ophthalmol. Vis. Sci. 2007;48(6):2667-2675. doi: 10.1167/iovs.06-1383.
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purpose. To identify costimulatory molecules that are important in the effector phase of experimental autoimmune uveitis (EAU).
methods. EAU was induced in C57BL/6 (B6) mice by transfer of activated T cells specific for the interphotoreceptor-binding protein (IRBP) 1-20 peptide. The animals were then treated with and without anti-leukocyte function associated antigen (LFA)-1α mAb, at day 0 or 10 (disease onset) after T-cell transfer. Clinical signs of inflammation, ocular histology, and infiltrated inflammatory cells in the eye were compared. The primary and secondary proliferative responses of uveitogenic CD4 and CD8 T cells were tested after treatment with costimulatory blockers in vivo and in vitro. Moreover, the abilities of uveitogenic T cell trafficking and their interaction with retinal astrocytes were examined.
results. Anti-LFA-1α Abs caused significant suppression of disease when administered either at the time of effector uveitogenic T cell transfer or at disease onset. Studies of the mechanisms by which anti-LFA-1α Ab inhibits the effector phase of uveitis demonstrated that it blocks multiple pathogenic events of uveitis mediated by IRBP-specific uveitogenic T cells, including the activation of T cells outside and inside the eye and the trafficking of activated autoreactive T cells into the inflammatory site. In addition, Ab treatment selectively suppressed the activation and expansion of pathogenic, but not regulatory, T cells in vivo.
conclusions. Anti-LFA-1α Abs are potent inhibitors of established autoimmune uveitis and that such treatment may be applicable not only for the prevention, but also the treatment, of T-cell–mediated autoimmune diseases.
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