Glatiramer acetate (Copaxone®) induces degenerate, Th2-polarized immune responses in patients with multiple sclerosis
Petra W. Duda, … , Jeffrey I. Krieger, David A. Hafler
Petra W. Duda, … , Jeffrey I. Krieger, David A. Hafler
Published April 1, 2000
Citation Information: J Clin Invest. 2000;105(7):967-976. https://doi.org/10.1172/JCI8970.
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Article

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

Abstract

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.

Authors

Petra W. Duda, Mascha C. Schmied, Sandra L. Cook, Jeffrey I. Krieger, David A. Hafler

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IL-13 secretion is increased after daily injections of GA. Primary T-cel...
IL-13 secretion is increased after daily injections of GA. Primary T-cell lines were set up in 10 identical wells each in the presence of no antigen or with 1.0, 10, and 100 μg/mL GA and cultured as described in Methods. Identical wells were pooled on day 11, and 30,000 T cells each were restimulated with no antigen or 1.0, 10, and 100 μg/mL GA pulsed on 100,000 autologous APCs. Cytokines were measured in supernatants by ELISA after 48 hours as described, and proliferation was measured by [3H]thymidine incorporation. Asterisks point at values that were above the upper limit of detection of the IL-13 assay of 10,000 pg/mL.