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B. P. Vistica, H. Yin, C.-C. Chan, J. L. Strominger, I. Gery; Comparison of Amino Acid Copolymers Glatiramer Acetate (GA) and poly(Y, F, A, K)n in Inhibition of Development of Experimental Autoimmune Uveitis (EAU) and Related Immune Responses. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4764.
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GA, also known as Copaxone [poly(Y, E, A, K)n] is a synthetic amino acid copolymer that is widely prescribed for treatment of multiple sclerosis. GA has been shown to inhibit experimental autoimmune encephalomyelitis (EAE) mainly by induction of regulatory cells, as well as a possible involvement of antigen competition. A novel copolymer, poly(Y, F, A, K)n called YFAK, was found to surpass GA in its immunomodulatory activity in EAE. Here, we compared GA and YFAK for their capacity to inhibit EAU and related immune responses.
The suppressive activities of GA and YFAK were examined by two procedures: (i) inhibition of EAU, tested by incorporation of the copolymers in the antigen/CFA emulsion ("co-immunization") and monitoring inhibition of EAU and cellular immune responses against the immunizing antigen (IRBP or its peptide 161-180); (ii) generation of T cell lines specific for GA or YFAK and testing their immunosuppressive activity in vivo by adoptive transfer to inhibit development of EAU and immune response in recipients, and in vitro by the inhibitory effect of these cell lines on lymphocyte proliferation.
When administered by co-immunization, YFAK inhibited EAU and lymphocyte proliferation and IFNγ or IL-17 secretion to IRBP or its peptide 161-180 more effectively than GA in both B10.RIIl and B10.A mice. T cell lines specific for YFAK were more inhibitory to EAU than GA-specific lines, both in vivo and in vitro, an effect that could be attributed, at least in part, to their production of exceedingly high levels of Th2 cytokines, in particular IL-4, IL-10, and IL-13. In addition, the treatment with YFAK or GA did not change the level of natural regulatory T cells (CD4+CD25+FoxP3+).
Both GA and the novel copolymer, YFAK, inhibited development of EAU and related immune responses in mice. In direct comparison, YFAK was far more effective than GA.
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