Glatiramer acetate (Copaxone) induces degenerate, Th2-polarized immune responses in patients with multiple sclerosis.
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.
Duda
P W
PW
Laboratory of Molecular Immunology, Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Schmied
M C
MC
Cook
S L
SL
Krieger
J I
JI
Hafler
D A
DA
D000328:Adult; D000595:Amino Acid Sequence; D002455:Cell Division; D002478:Cells, Cultured; D003429:Cross Reactions; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D000068717:Glatiramer Acetate; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D007371:Interferon-gamma / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008024:Ligands; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000276:immunology*; D004676:Myelin Basic Protein / Q000276:immunology; D009186:Myelin Sheath / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D013745:Tetanus Toxoid / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology
D018984:Epitopes, T-Lymphocyte; D016056:Immunodominant Epitopes; D007166:Immunosuppressive Agents; D015848:Interleukin-5; D008024:Ligands; D004676:Myelin Basic Protein; D010446:Peptide Fragments; D010455:Peptides; D013745:Tetanus Toxoid; C407155:myelin basic protein 84-102; D000068717:Glatiramer Acetate; D007371:Interferon-gamma