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Hiroshi Keino, Yasuhiko Sato, Annabelle Okada; IL-2/IL-2 Ab complex plus rapamycin ameliorate experimental autoimmune uveoretinitis associated with expansion of CD4+Foxp3+ regulatory T cells. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2024.
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To determine whether injection of IL-2/IL-2Ab together with rapamycin is effective in reducing ocular inflammation in experimental autoimmune uveoretinitis (EAU).
C57BL/6J mice were immunized with human interphotoreceptor retinoid binding protein peptide (h-IRBP1-20). Mice were injected i.p. with PBS, IL-2/IL-2Ab (JES6-1), rapamycin, or IL-2/IL-2Ab plus rapamycin on days 1, 2, 3, and 4 after immunization. Fundus examination was performed on days 9, 12, 15, 18, and 21 after immunization. The expression of Foxp3 on CD4+ T cells from draining lymph nodes (LNs) was examined by flow cytometry on day 7.
Injection of IL-2/IL-2Ab plus rapamycin significantly reduced the clinical score of EAU on days 12, 15 and 18 compared to PBS, IL-2/IL-2Ab, or rapamycin treated mice. In addition, mice treated with IL-2/IL-2Ab plus rapamycin showed decreased severity of EAU by histopathological analysis. Although the expansion of CD4+Foxp3+ regulatory T cells (Tregs) was observed on day 7 in draining LNs from IL-2/IL-2Ab, rapamycin, and IL-2/IL-2Ab plus rapamycin treated mice, the expansion of Tregs was most prominent in IL-2/IL-2Ab plus rapamycin treated mice.
These results indicate that injection of IL-2/IL-2Ab plus rapamycin is effective in reducing ocular inflammation in EAU and in inducing the expansion of CD4+Foxp3+ Tregs. In vivo expansion of T regs using IL-2/IL-2Ab plus rapamycin may have clinical potential for the treatment of human refractory uveitis.
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