TY - JOUR
T1 - Glatiramer acetate (Copaxone) therapy induces CD8+ T cell responses in patients with multiple sclerosis
AU - Karandikar, Nitin J.
AU - Crawford, Michael P.
AU - Yan, Shirley X
AU - Ratts, Robert B.
AU - Brenchley, Jason M.
AU - Ambrozak, David R.
AU - Lovett-Racke, Amy E.
AU - Frohman, Elliot
AU - Stastny, Peter
AU - Douek, Daniel C.
AU - Koup, Richard A.
AU - Racke, Michael K.
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
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U2 - 10.1172/JCI200214380
DO - 10.1172/JCI200214380
M3 - Article
C2 - 11877472
AN - SCOPUS:0036195878
SN - 0021-9738
VL - 109
SP - 641
EP - 649
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 5
ER -