Amino acid copolymer-specific IL-10-secreting regulatory T cells that ameliorate autoimmune diseases in mice

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Abstract
IL-10-secreting regulatory T cell lines specific to glatiramer acetate [poly(Y,E,A,K)n] or poly(Y,F,A,K)n have been established from the enlarged spleen and lymph nodes that result from copolymer treatment of SJL mice in which experimental autoimmune encephalomyelitis was induced by PLP139-151. These CD4+CD25+T cell lines secrete high levels of IL-10 and IL-13 but only small amounts of IL-4 and virtually no TGF-beta, IL-17, IL-6, IFN-gamma, or TNF-alpha. Their phenotypes are particularly characterized by the absence of Foxp3 and the presence of two TNFR family members, CD30 and GITR. The lines proliferated specifically to the immunizing copolymers but were autoantigen-nonspecific, in that the same T cell line could suppress autoimmunity induced by three different autoantigens in SJL mice, i.e., PLP139-151(EAE), MBP85-99 (EAE), and bovine peripheral nerve myelin (experimental autoimmune neuritis), indicating they function by bystander suppression.