Inhibition of experimental autoimmune uveitis by amino acid copolymers.
Glatiramer acetate (GA), a synthetic random amino acid copolymer, poly(Y, E, A, K)n, is widely used for treatment of multiple sclerosis. It inhibits experimental autoimmune encephalomyelitis (EAE) in mice by competition with the antigen and by induction of regulatory T cells. A novel copolymer, poly (F, Y, A, K)n , designated FYAK, was more effective than GA in its immunomodulatory activity in EAE. Here, FYAK and GA were compared in the amelioration of another disease model in mice, experimental autoimmune uveoretinitis (EAU). When tested by co-immunization with an uveitogenic antigen, FYAK was superior to GA in its capacity to inhibit EAU induction, as well as immune processes related to this condition. Further, regulatory T-cell lines specific to FYAK were more immunosuppressive than GA-specific lines in the EAU model. The superiority of FYAK-specific lines was accompanied by higher production of Th2 cytokines. These data thus demonstrate that FYAK, a novel copolymer, is superior to GA in its capacity to inhibit immunopathogenic processes in a non-central nervous system tissue.
Yin
Hongen
H
Laboratory of Immunology, National Eye Institute, Bethesda, MD 20892, USA.
Vistica
Barbara P
BP
Chan
Chi-Chao
CC
Strominger
Jack L
JL
Gery
Igal
I
D000596:Amino Acids / Q000627:therapeutic use*; D000818:Animals; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005260:Female; D000068717:Glatiramer Acetate; D051379:Mice; D020721:Nervous System Autoimmune Disease, Experimental / Q000276:immunology* / Q000517:prevention & control*; D010455:Peptides / Q000627:therapeutic use*; D011108:Polymers / Q000627:therapeutic use; D014605:Uveitis / Q000276:immunology* / Q000517:prevention & control*
D000596:Amino Acids; D010455:Peptides; D011108:Polymers; D000068717:Glatiramer Acetate