Research
Dissecting immune mechanism of Copaxone
Glatiramer acetate (Copaxone®), a synthetic copolymer of four amino acids (alanine, glutamic acid, lysine, and tyrosine), is an approved immunomodulatory therapy for patients with relapsing-remitting MS. Copaxone is known to prime T-cell responses in treated patients. However, the nature of these responses, their role in immunomodulating the disease and the mechanisms by which Copaxone exerts its effects are presently unclear. Recent studies from our laboratory provide the first direct evidence of a potent CD8+ T cell response in human subjects. Copaxone-reactive CD8+ T cell responses are deficient in untreated MS patients, compared to healthy individuals. Following Copaxone therapy, these responses are upregulated and restored to levels found in healthy subjects. These cells appear to mediate their immunomodulatory effects by direct cytotoxic killing of activated CD4+ T-cells. Based on these observations, we hypothesize that Copaxone-induced CD8+ T cell responses play an important role in the immunomodulatory effect of the drug and are now building on our studies to delineate their mechanism in both human MS and its animal model.
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Karandikar, N., Crawford, M., Yan, X., Nitin J. Karandikar, Michael P. Crawford, Yan, X., Ratts, R., Brenchley, J., Ambrozak, D., Lovett-Racke, A., Frohman, E., Stastny, P., Douek, D., Koup, R. and Racke, M. (2002). Glatiramer acetate (Copaxone) therapy induces CD8+ T cell responses in patients with multiple sclerosis. J. Clin. Invest. 109:641–649.
Tennakoon, D., Mehta, R., Ortega, S., Bhoj, V., Racke, M., and Karandikar, N. (2006). Therapeutic Induction of Regulatory, Cytotoxic CD8+ T Cells in Multiple Sclerosis. J. Immunol., 176:7119–7129.