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- W914996913 abstract "OBJECTIVE: To elucidate the requirement for T-regulatory cells (Tregs) in the therapeutic activity of glatiramer acetate (GA) in the animal model of multiple sclerosis - experimental autoimmune encephalomyelitis (EAE). BACKGROUND: GA, a therapeutic agent for MS, induces a broad immunomodulatory effect on various immune subsets, resulting in a shift towards anti-inflammatory responses. Several studies demonstrated an effect of GA on Tregs, however, the role of these cells in its therapeutic effect has not been clarified. DESIGN/METHODS: Tregs were identified immunohistochemically in the CNS of EAE-induced mice. The ability of GA to ameliorate EAE was tested in Foxp3GFPLuciDTR-4 transgenic mice, in which Tregs express diphtheria toxin (DT) receptor, facilitating their selective depletion. GA or PBS were injected for 7 days following EAE induction. DT was injected one and two days after treatment conclusion. Flow cytometry was used to verify Tregs depletion. RESULTS: Immunohistological analysis revealed 2-fold elevation in the number of CD3+Foxp3+ Tregs in the CNS of EAE-mice following GA treatment. GA drastically reduced disease manifestation in wild type mice, and its effect was not abrogated by DT injection (maximal clinical score 0.5 in GA-treated compared to 2.9 in untreated mice). In mice carrying the Foxp3GFPLuciDTR-4 transgene injected with DT, GA was less effective than in wild type mice. Yet, even in these mice, the clinical score of the GA-treated was lower than in the untreated mice (1.6 and 3.0, respectively). CONCLUSIONS: GA induces elevation of Tregs. Selective depletion of Tregs reduces but does not eliminate the ability of GA to ameliorate EAE. These findings support the role of Tregs, but not in an exclusive fashion, in the therapeutic effect of GA. Study Supported by: Teva Disclosure: Dr. Aharoni has received research support from Teva Neuroscience. Dr. Tali has nothing to disclose. Dr. Shakhar has nothing to disclose. Dr. Sela has received royalty payments from Teva Neuroscience. Dr. Arnon has received royalty payments from Teva." @default.
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- W914996913 date "2015-04-06" @default.
- W914996913 modified "2023-09-26" @default.
- W914996913 title "Selective depletion of T regulatory cells reduces but does not eliminate the ability of glatiramer acetate to ameliorate experimental autoimmune encephalomyelitis (P2.192)" @default.
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