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Y. Ke; Reversal of Established Autoimmune Uveitis Upon Blockade of the Lfa-1/Intercellular Adhesion Molecule-1 (icam-1) Pathway. Invest. Ophthalmol. Vis. Sci. 2007;48(13):2633.
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© ARVO (1962-2015); The Authors (2016-present)
To identify costimulatory molecules that are important for the effector phase of experimental autoimmune uveitis. (EAU).
EAU was induced in C57BL/6 (B6) mice by transfer of activated T cells specific for interphotoreceptor binding protein (IRBP) 1-20 peptide. The animals were then treated with and without anti-LFA-1 mAb, at day 0 or day 10 (disease onset) post-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 also examined.
Anti LFA-1 Abs cause 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-1 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.
Anti-LFA-1 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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