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Glatiramer acetate (Copaxone) therapy induces CD8+ T cell responses in patients with multiple sclerosis
Nitin J. Karandikar, … , Richard A. Koup, Michael K. Racke
Nitin J. Karandikar, … , Richard A. Koup, Michael K. Racke
Published March 1, 2002
Citation Information: J Clin Invest. 2002;109(5):641-649. https://doi.org/10.1172/JCI14380.
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Article Immunology

Glatiramer acetate (Copaxone) therapy induces CD8+ T cell responses in patients with multiple sclerosis

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Abstract

Glatiramer acetate (GA; Copaxone) is a random copolymer of glutamic acid, lysine, alanine, and tyrosine that is used therapeutically in patients with multiple sclerosis (MS). To investigate the mechanism of the drug’s immunomodulatory effect, we used immunophenotypic approaches to characterize the precise nature of GA-induced T cell responses. We demonstrate here that healthy individuals and untreated MS patients exhibit prominent T cell proliferative responses to GA. However, these responses are different in distinct subsets of T cells. Whereas GA-induced CD4+ T cell responses are comparable in healthy individuals and MS patients, CD8+ T cell responses are significantly lower in untreated MS patients. Treatment with GA results in upregulation of these CD8+ responses with restoration to levels observed in healthy individuals. Both CD4+ and CD8+ GA-specific responses are HLA-restricted. GA therapy also induces a change in the cytokine profile of GA-specific CD4+ and CD8+ T cells. This study provides the first direct immunophenotypic evidence, to our knowledge, of GA-specific CD8+ T cell responses and their upregulation during the course of therapy, which may suggest a role for these responses in the immunomodulatory effects of the drug.

Authors

Nitin J. Karandikar, Michael P. Crawford, Xiao Yan, Robert B. Ratts, Jason M. Brenchley, David R. Ambrozak, Amy E. Lovett-Racke, Elliot M. Frohman, Peter Stastny, Daniel C. Douek, Richard A. Koup, Michael K. Racke

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Figure 5

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Intracellular cytokine staining of GA-specific CD4+ and CD8+ T cells. PB...
Intracellular cytokine staining of GA-specific CD4+ and CD8+ T cells. PBMCs were obtained from patient no. MS3 before treatment and at 3 months after the initiation of GA therapy. The cells were stained with CFSE and cultured in the presence of GA. On day 7 of culture, the cells were restimulated for 4 hours with PMA and ionomycin in the presence of brefeldin A and then stained for surface CD4 and CD8 and intracellular cytokine (IFN-γ, TNF-α, or IL-4), as indicated. The data are gated for either CD4+ (left six panels) or CD8+ T cells (right six panels) and show CFSE staining on the x axis and cytokine staining on the y axis. The cutoff was based on staining with isotypic control antibodies. The population in black represents the cytokine-producing, GA-specific cells (i.e., cells within the proliferating fraction). The number indicates the percentage of the GA-specific (proliferating) cells that were positive for the indicated cytokines. As individual cytokine staining was performed in different tubes, it is not possible to assess whether the same or distinct subsets of cells produced the different cytokines.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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