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

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

Research output: Contribution to journalArticle

156 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)641-649
Number of pages9
JournalJournal of Clinical Investigation
Volume109
Issue number5
DOIs
StatePublished - 2002

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Multiple Sclerosis
T-Lymphocytes
Up-Regulation
Therapeutics
T-Lymphocyte Subsets
Pharmaceutical Preparations
Lysine
Tyrosine
Glatiramer Acetate
Cytokines

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Karandikar, N. J., Crawford, M. P., Yan, S. X., Ratts, R. B., Brenchley, J. M., Ambrozak, D. R., ... Racke, M. K. (2002). Glatiramer acetate (Copaxone) therapy induces CD8+ T cell responses in patients with multiple sclerosis. Journal of Clinical Investigation, 109(5), 641-649. https://doi.org/10.1172/JCI200214380

Glatiramer acetate (Copaxone) therapy induces CD8+ T cell responses in patients with multiple sclerosis. / Karandikar, Nitin J.; Crawford, Michael P.; Yan, Shirley X; Ratts, Robert B.; Brenchley, Jason M.; Ambrozak, David R.; Lovett-Racke, Amy E.; Frohman, Elliot; Stastny, Peter; Douek, Daniel C.; Koup, Richard A.; Racke, Michael K.

In: Journal of Clinical Investigation, Vol. 109, No. 5, 2002, p. 641-649.

Research output: Contribution to journalArticle

Karandikar, NJ, Crawford, MP, Yan, SX, Ratts, RB, Brenchley, JM, Ambrozak, DR, Lovett-Racke, AE, Frohman, E, Stastny, P, Douek, DC, Koup, RA & Racke, MK 2002, 'Glatiramer acetate (Copaxone) therapy induces CD8+ T cell responses in patients with multiple sclerosis', Journal of Clinical Investigation, vol. 109, no. 5, pp. 641-649. https://doi.org/10.1172/JCI200214380
Karandikar, Nitin J. ; Crawford, Michael P. ; Yan, Shirley X ; Ratts, Robert B. ; Brenchley, Jason M. ; Ambrozak, David R. ; Lovett-Racke, Amy E. ; Frohman, Elliot ; Stastny, Peter ; Douek, Daniel C. ; Koup, Richard A. ; Racke, Michael K. / Glatiramer acetate (Copaxone) therapy induces CD8+ T cell responses in patients with multiple sclerosis. In: Journal of Clinical Investigation. 2002 ; Vol. 109, No. 5. pp. 641-649.
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