Glatiramer acetate (Copaxone®) induces degenerate, Th2-polarized immune responses in patients with multiple sclerosis

• Published in: The Journal of clinical investigation Vol. 105; no. 7; pp. 967 - 976
• Main Authors: Duda, Petra W., Schmied, Mascha C., Cook, Sandra L., Krieger, Jeffrey I., Hafler, David A.
• Format: Journal Article
• Language: English
• Published: United States American Society for Clinical Investigation 01.04.2000
• Subjects: Adult; Amino Acid Sequence; Cell Division; Cells, Cultured; Cross Reactions; Epitopes, T-Lymphocyte - immunology; Female; Glatiramer Acetate; Humans; Immunodominant Epitopes - immunology; Immunosuppressive Agents - administration & dosage; Immunosuppressive Agents - pharmacology; Immunosuppressive Agents - therapeutic use; Interferon-gamma - secretion; Interleukin-5 - secretion; Leukocytes, Mononuclear - cytology; Ligands; Male; Middle Aged; Molecular Sequence Data; Multiple Sclerosis - drug therapy; Multiple Sclerosis - immunology; Myelin Basic Protein - immunology; Myelin Sheath - immunology; Peptide Fragments - immunology; Peptides - administration & dosage; Peptides - pharmacology; Peptides - therapeutic use; Tetanus Toxoid - immunology; Th2 Cells - drug effects; Th2 Cells - immunology
• ISSN: 0021-9738; 1558-8238
• DOI: 10.1172/JCI8970

We examined the effect of glatiramer acetate, a random copolymer of alanine, lysine, glutamic acid, and tyrosine, on antigen-specific T-cell responses in patients with multiple sclerosis (MS). Glatiramer acetate (Copaxone) functioned as a universal antigen, inducing proliferation, independent of any prior exposure to the polymer, in T-cell lines prepared from MS or healthy subjects. However, for most patients, daily injections of glatiramer acetate abolished this T-cell response and promoted the secretion of IL-5 and IL-13, which are characteristic of Th2 cells. The surviving glatiramer acetate-reactive T cells exhibited a greater degree of degeneracy as measured by cross-reactive responses to combinatorial peptide libraries. Thus, it appears that, in some individuals, in vivo administration of glatiramer acetate induces highly cross-reactive T cells that secrete Th2 cytokines. To our knowledge, glatiramer acetate is the first agent that suppresses human autoimmune disease and alters immune function by engaging the T-cell receptor. This compound may be useful in a variety of autoimmune disorders in which immune deviation to a Th2 type of response is desirable.