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

PW Duda, MC Schmied, SL Cook… - The Journal of …, 2000 - Am Soc Clin Investig
PW Duda, MC Schmied, SL Cook, JI Krieger, DA Hafler
The Journal of clinical investigation, 2000Am Soc Clin Investig
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 …
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.
The Journal of Clinical Investigation