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Rose Mathew, Sheng Min Hsu, Joan Stein-Streilein; Acaid Transfer Therapy For EAU. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2264.
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Previous studies in the laboratory showed that autoimmune inflammation in mice could be suppressed by transfer of TGFβ treated IRBP specific tolerogenic antigen presenting cells (Tol APC). The transfer of Tol APC reduced the clinical symptoms of on going EAU. To further study this result we examined if the tolerance could be transferred by T cells harvested from Tol APC treated EAU mice. To make the tolerogenic therapy applicable for human uveitis we tested if extract of retina (target tissue) as antigen to pulse Tol APC could be used.
Splenic and lymph node T cells from IRBP immunized mice were enriched, pulsed invitro with IRBP 1-20 and transferred to naïve mice to induce EAU. On day seven, tolerogenic APC were injected iv. Three weeks after adoptive transfer, CD4+ or CD8+ T cells were collected, enriched using magnetic beads and transferred into another group of EAU mice. Inflammation of the retina was evaluated twice a week using a slit lamp for five weeks. For preparing retinal extract, mouse eyes were cut in half along the equator and the retina was gently peeled off from the posterior part, placed into serum free medium and sonicated. The mice were treated with APC pulsed with retinal extract seven days after EAU induction and were evaluated for severity of EAU progression.
We found that tolerance could be transferred to another group of EAU mice with CD8+ (but not CD4+) T cells harvested from the Tol-APC treated EAU mice. We also observed retinal extract pulsed Tol APC effectively suppressed adoptively transferred EAU.
IRBP pulsed Tol APC were able to suppress ongoing EAU by inducing CD8+ T reg cells that altered the clinical symptoms of autoimmune inflammation in the eye. Retinal extract pulsed Tol APC treated mice had significantly lower scores and incidence of EAU compared to untreated mice. The ability to use retinal extract as antigens raises the possibility of ACAID therapy being used in human uveitis where the antigen is unknown. This research was supported in part by NIH grant: EY011983, EY020614
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