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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Figure 1

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The proliferative response to GA is decreased on average after daily inj...
The proliferative response to GA is decreased on average after daily injections of GA. The antigen-specific proliferative response of 20 or 30 primary T-cell lines induced with 40 μg/mL GA as described in Methods was measured by split-well assay for each patient at each time point. Before and at 6 months of treatment, all 7 patients could be tested; at 3 and 12 months, data for 5 patients were obtained. (a) Each panel represents data from an individual patient. Squares represent mean ± SEM proliferation in Δ cpm of the GA-specific response compared with the no-antigen control. Background levels of the [3H]thymidine incorporation for all patients of the no-antigen condition were 1,747 ± 111 before treatment, and 3,286 ± 175, 3,785 ± 262, and 3,509 ± 239 at 3, 6, and 12 months of treatment, respectively. The numbers in the figure indicate the SI over the no-antigen control for each time point. (b) The mean stimulation index SI ± SEM for all T-cell lines from all patients tested at each time point is shown.